Devices, systems and methods for tissue analysis, locaton determination and tissue ablation

ABSTRACT

An exemplary tissue detection and location identification apparatus can include, for example, a first electrically conductive layer at least partially (e.g., circumferentially) surrounding a lumen, an insulating layer at least partially (e.g., circumferentially) surrounding the first electrically conductive layer, and a second electrically conductive layer circumferentially surrounding the insulating layer, where the insulating layer can electrically isolate the first electrically conductive layer from the second electrically conductive layer. A further insulating layer can be included which can at least partially surrounding the second electrically conductive layer. The first electrically conductive layer, the insulating layer, and the second electrically conductive layer can form a structure which has a first side and a second side disposed opposite to the first side with respect to the lumen, where the first side can be longer than the second side thereby forming a sharp pointed end via the first side at a distal-most portion. The exemplary configuration can be used for (a) determination/detection of a tissue type using impendence of the electrically conductive layers, and/or (ii) determination of a location of at least one portion of the insertion device/apparatus. Based on such determination, it is possible to effectuate ablation or heating of tissue by applying RF energy across the electrically conductive layers.

CROSS-REFERENCE TO RELATED APPLICATION(S)

This application relates to and claims priority from U.S. PatentApplication Ser. No. 62/941,213 filed on Nov. 27, 2019, the entiredisclosure of which is incorporated herein by reference.

FIELD OF THE DISCLOSURE

The present disclosure relates generally to a detection or sensing of ananimal or human tissue type, determination/inference or a location of aportion of an insertion arrangement and application of ablative causingsignals, and more specifically, to exemplary embodiments of exemplaryapparatus, devices and systems, which can be integrated into one or moreinsertion devices (e.g., including but not limited to a needle, cannula,etc.), for determining a tissue or fluid type prior to (i) an injectionof any substance or material (e.g., drugs, biologics, filler,therapeutics, cellular materials, cells, genetic materials, stem cells,immunotherapy agents, etc.) and/or (i) an aspiration of fluids orcollection of materials or tissue (e.g., core biopsy) from a body viasuch insertion apparatus, and to exemplary methods for manufacturingsuch insertion apparatus and/or sensing or determining the tissue typeupon the insertion thereof. The present disclosure is also directed toexemplary embodiments of exemplary apparatus, devices and systems, whichcan be integrated into one or more insertion devices (e.g., includingbut not limited to an endoscope(s), catheter(s), laparoscope(s), etc.)via optical radiation transmitter(s) analysis, imaging, positioningand/or therapy of tissue using optical (e.g., including but not limitedto light) radiation. The exemplary embodiments of exemplary apparatus,devices and systems can also (i) generate and/or apply radio frequency(RF) signals to the tissue to heat the target tissue via at least someof the same sensing devices and/or electrode used from the determinationof the tissue type, and (ii) determine and/or infer a position of, e.g.,a tip or another portion of an insertion apparatus/device inthree-dimensional space, e.g., using at least some of the samecomponents utilized for the tissue detection and/or the RF signalapplication.

BACKGROUND INFORMATION

When performing surgery or procedure on a animal or human subject, orinjecting any substance(s) and/or or material(s), including but notlimited a pharmacological agents (e.g., a drug), filler substances,biological and non biological fillers, therapeutics, tissue or cellularmaterial, stem cells, genetic materials, immunotherapy agents, etc. intoan animal or human subject, it can be beneficial to inject the materialinto a particular tissue of the subject (e.g., certain blood vessels,fat, muscle, etc.) in some applications. It can also be important orbeneficial to not inject the materials into certain tissue or lumen inthe subject (e.g., certain blood vessels, etc.), in some applications,while being beneficial to inject such materials in such tissue or lumensin other applications. There are a number of commercially availablenon-invasive visualization systems (including ultrasound and opticalvisualization devices, etc.) to help identify and access specificstructures such as veins or arteries (phlebotomy, IV, etc.). One exampleis the AccuVein which incorporates an infrared light source and detectorwhich provide visualization of shallow veins. There are, however, noknown technologies which are integrated with such access devices capableof specifically sensing or tissue changes or detecting blood vessels forthe purpose of vessel targeting or avoidance.

Various (e.g., non-insertion) technologies exist for relatedapplications, for example: (i) detecting blood vessels for the purposeof injection or blood collection, and (ii) detecting when a needle haspenetrated a specific type of tissue (e.g., spinal space or other).However, there are no known insertion devices/arrangements thatintegrate sensing electrodes that facilitate rapid or real-timesensing/detection of different tissue types, while also facilitating aninjection of substances or materials into a body and/or an aspiration offluids or collection of material, cells or tissues from the body, suchas, e.g., pharmacological agents, fillers, biologics, therapeutics,cellular materials, stem cells, genetic materials, immunotherapy agents,substances, etc., for example, with no manipulation of the insertiondevices/arrangements.

One company, Injeq, created an IQ-Needle, which is a needle that useselectrical impedance spectroscopy to detect various tissue types, forexample, to detect when the needle has penetrated spinal fluid. Theneedle incorporates two electrodes; one electrode is incorporated into aneedle, and the other is incorporated into a stylet located inside theneedle. After the target location has been detected, the stylet needs tobe removed and then a syringe or other device must be connected to theneedle before the procedure (e.g., injection or fluid collection) canbegin. The IQ-Needle is shown and described in U.S. Patent PublicationNo. 2016/0029920, the entire disclosure of which is incorporated hereinby reference in its entirety. Injeq has also developed a biopsy needlethat uses the same approach. (See, e.g., U.S. Patent Publication No.2018/0296197, the entire disclosure of which is incorporated herein byreference in its entirety).

Another prior system includes a sensing needle incorporatinginterdigitated, co-planar, electrodes on the surface for identifyingdifferent tissues using electrical impedance spectroscopy. Theelectrodes are deposited directly on the needle using conventionalprinted circuit board fabrication techniques. In such system, however,the needle is closed. Thus, the needle can only be used for sensing, andnot for injecting an agent into a subject. Additionally, the needle istethered to an analyzer used to determine the tissue type. Finally,since the electrodes are on the outer circumferential surface of theneedle, the electrodes are not co-located with the tip. Therefore, themeasurements from the electrodes do not reflect the conditions at thetip.

Additionally, many minimally invasive procedures involve devices, suchas needles or catheters, which use external imaging to guide deviceswithin the body. Imaging techniques include ultrasound, X-rays, magneticresonance imaging (MRI), etc. Ultrasound imaging has been shown to be aneffective guidance technology, although it provides only atwo-dimensional (2D) image with limited information and somewhat poorneedle visualization (See, e.g., Rocha et al., “Step-by-step ofultrasound-guided core-needle biopsy of the breast: review andtechnique,” Radiol Bras. 2013 July/Ago; Vol. 46(4), pages 234-241).Further, X-ray or computerized tomography (CT) scans expose both theclinician and the subject to unwanted radiation. Thus, X-ray, CT, andMRI equipment is typically centralized with scheduling limitations. Itis indeed difficult to provide a three-dimensional (3D) location of thetissue using the existing technology, and also limiting the negativeeffects of the devices that are needed to obtain the location.

Additionally, MRI, x-rays, ultrasound, and optics have all foundimportant roles in imaging applications. In many applications opticalradiation to effectuate imaging, analysis, therapy and otherapplications can offers certain advantages over other approaches becauseit is non-ionizing, non-contact, and can achieve high resolution. Thereare a variety of types of optical techniques, which utilize optical(e.g., light) radiation delivery, that are currently available include,e.g., optical coherence tomography (OCT) and other interferometricimaging techniques.

Concentric electrode configurations can facilitate highly localizedradio-frequency (RF) (radiofrequency) ablation at the tip of the deviceand/or at the electrode. RF ablation have been used in surgicalapplications to cut and coagulate tissue. (See, e.g., Covidien,“Principles of Electrosurgery,” Boulder Colo., 2008). RF ablationgenerally requires the use of at two electrodes, i.e., an activeelectrode and a return electrode. Alternating current at RF frequenciespass from one electrode through the tissue to the second electrode. Thecurrent causes resistive heating of the tissue.

Monopolar surgical instruments incorporate a single active electrode.The return electrode generally includes a pad placed somewhereexternally to the body. The current is concentrated near the activeelectrode but spreads quickly as it spreads through the body to thereturn and so the heating should be limited to the area around theactive electrode. The effect of the electrical current can be adjustedby varying the magnitude, duty cycle, and frequency. In practice, e.g.,it is possible to provide heating around the return electrode pad, oftenleading to burns on the body.

Bipolar surgical instrument incorporates two electrodes, typicallyprovided close together so that current passes directly from oneelectrode to the other. An example of such instrument includes bipolarforceps, in which the two electrodes are placed on each of the two jaws.Current passes through any tissue between the two jaws. While bipolarinstruments have a highly localized effect, unfortunately, they are morecomplicated to make than the monopolar instruments because of the needto insulate and isolate the two electrodes.

Optical (e.g., light) radiation delivery inside the body can beperformed using discrete fibers which can be integrated into a medicalinsertion device, such as a catheter. These exemplary applications caninclude intravascular OCT (as described in, e.g., Bouma et al.,“Intravascular optical coherence tomography,” Biomedical Optics Express2660, Vol. 8, No. 5, May 1, 2017), optical spectroscopy (as describedin, e.g., Utzinger et al., “Fiber Optic Probes For Biomedical OpticalSpectroscopy,” J. of Biomedical Optics, 8(1), (2003)), and cardiacablation (as described in, e.g., Dukkipati et al., “Pulmonary VeinIsolation Using The Visually Guided Laser Balloon: A Prospective,Multicenter, And Randomized Comparison To Standard RadiofrequencyAblation,” JACC, 66(12):1350-60 (2015)). Other exemplary techniquesinclude, e.g., and other spectroscopic imaging techniques, Ramanimaging, diffuse-wave optical imaging, and two-photon imagingtechniques. OCT is an interferometric imaging technology and thus hasthe properties of very high sensitivity and large dynamic range. OCTachieves depth resolution via a combination of the focal properties ofthe imaging optics used and the coherence properties of the opticalsource used.

Additionally, many minimally invasive procedures involve devices, suchas needles or catheters, which use external imaging to guide deviceswithin the body. Imaging techniques include ultrasound, X-rays, magneticresonance imaging (MRI), etc. Ultrasound imaging has been shown to be aneffective guidance technology, although it provides only atwo-dimensional (2D) image with limited information and somewhat poorneedle visualization (See, e.g., Rocha et al., Rafael Dahmer, Pinto,Renata Reis, Tavares, Diogo Paes Barreto Aquino, Gonçalves, CláudiaSofia Aires, “Step-by-step of ultrasound-guided core-needle biopsy ofthe breast: review and technique,” Radiol Bras. 2013 July/Ago;46(4):234-241). Further, X-ray or computerized tomography (CT) scansexpose both the clinician and the patient to unwanted radiation. Thus,X-ray, CT, and Mill equipment is typically centralized with schedulinglimitations. It is indeed difficult to provide a three-dimensional (3D)location of the tissue using the existing technology, and also limitingthe negative effects of the devices that are needed to obtain thelocation.

Further, the configurations and components of the catheters whichutilize such optical modalities, including OCT, CT, MM, fluorescenceimaging Raman, optical imaging, etc. can be complex and costly. Variousmedical procedures which utilize catheters require multiple exchanges ofdevices for and in the catheter, in which a guide wire or guide sheathare introduced into the catheter first, and then ancillary tools, forexample, a transseptal needle, can be inserted over or within thewire/sheath. These tools are then generally removed and exchanged foranalysis and/or treatment tools, and/or entirely by sensing/treatmentcatheters.

Such exchange of components and/or tools can be length, and may affectthe medical procedure when the timing of the use of the catheter and/ortools thereof can be important, and sometimes even crucial.

Thus, it may be beneficial to provide exemplary apparatus, devices andsystems, which can be integrated into a one or more insertion devices(e.g., including but not limited to one or more needles, cannulas,catheters, etc.) for:

-   -   determining a tissue type prior to and/or during (i) an        injection of any substance or material (e.g., such as, e.g.,        pharmacological agents, biologics, fillers, therapeutics,        cellular materials, stem cells, genetic materials, immunotherapy        agents, substances, etc.) and/or (ii) an aspiration of fluids,        substances, materials, cells, or tissues from a body via such        insertion apparatus, and to exemplary methods for manufacturing        such insertion apparatus and/or determining the tissue type upon        the insertion thereof,    -   generating and/or applying radio frequency (RF) signals to the        tissue to heat the target tissue via the same sensing devices        and/or electrode(s) which can be used for the determination of        the tissue type,    -   determining and/or inferring a position of a tip of an insertion        apparatus/device in three-dimensional space, e.g., using some of        the same components which can be used for the used for the        tissue type determination and/or the RF signal application,    -   providing optical radiation to the tissue, e.g., so as to        determine the tissue type and/or the position of the tip, and/or    -   ablating or otherwise effecting the tissue using components of        the insertion device(s), which can be based on the determination        of the tissue type and/or the position of the tip.        which can overcome at least some of the deficiencies described        herein above.

SUMMARY OF EXEMPLARY EMBODIMENTS

To that end, such exemplary apparatus, devices and systems can beprovided according to exemplary embodiments of the present disclosurewhich can include and/or utilize an insertion device/apparatus. Further,additional exemplary apparatus, devices and systems can be providedaccording to exemplary embodiments of the present disclosure which caninclude and/or utilize optical transmitter(s), including but not limitedoptical waveguide(s).

To that end, an exemplary insertion apparatus/device according to anexemplary embodiment of the present disclosure can include, for example,a first electrically conductive layer at least partially (e.g.circumferentially) surrounding a lumen, an insulating layer at leastpartially (e.g. circumferentially) surrounding the first electricallyconductive layer, and a second electrically conductive layer at leastpartially (e.g. circumferentially) surrounding the insulating layer,where the insulating layer can electrically isolate the firstelectrically conductive layer from the second electrically conductivelayer. A further insulating layer can be included which can at leastpartially (e.g. circumferentially) surrounding the second electricallyconductive layer. The first electrically conductive layer, theinsulating layer, and the second electrically conductive layer can forma structure which has a first side and a second side disposed oppositeto the first side with respect to the lumen, where the first side can belonger than the second side thereby forming a sharp pointed end via thefirst side at a distal-most portion of the insertion apparatus/device.The first electrically conductive layer, the insulating layer, and thesecond electrically conductive layer can form a structure that can bebeveled to form a sharp pointed end at a distal-most portion of theinsertion apparatus/device.

In some exemplary embodiments of the present disclosure, the firstelectrically conductive layer, the insulating layer, and the secondelectrically conductive layer can form a shaft of the insertionapparatus/device. The first electrically conductive layer, theinsulating layer, and the second electrically conductive layer can forma structure that can extend distally from a hub. A barrel can beconnected to the hub and a plunger can be configured to be inserted intothe barrel. The first electrically conductive layer can be configured totransmit and/or receive an electrical signal (e.g., a first electricalsignal), and the second electrically conductive layer can be configuredto transmit and/or receive the same or different electrical signal(e.g., the first and/or the second electrical signal), and acommunication device(s) can be configured to transmit informationrelated to the electrical signal(s). The communication device(s) can beembedded in one of (i) a hub of the insertion apparatus/device, or (ii)a barrel of the insertion apparatus/device.

In certain exemplary embodiments of the present disclosure, the firstelectrically conductive layer can be configured to transmit and/orreceive the electrical signal (e.g., a first electrical signal), and thesecond electrically conductive layer can be configured to transmitand/or receive the same or different electrical signal (e.g., the firstor the second electrical signal), and a hardware processing arrangementcan be configured to receive information related to the electricalsignal(s), determine an impedance based on the information, anddetermine a tissue or fluid type based on the impedance. An audiblearrangement can be configured to emit a sound based on the determinedtissue or fluid type. The audible arrangement may be augmented orreplaced by a visual arrangement to display a light or alphanumericoutput based on the determined tissue or fluid type. The processingarrangement can be embedded in (i) a hub of the insertionapparatus/device, and/or (ii) a barrel of the insertionapparatus/device. Alternatively, the processing arrangement may beremovably detachable from the hub or barrel. The lumen can be configuredto (i) have a pharmacological agent injected therethrough, or (ii) havea biopsy sample obtained therethrough.

According to a further exemplary embodiment of the present disclosure, aradiofrequency (RF) signal can be applied to the first electricallyconductive layer and/or the second electrically conductive layer, suchthe combination and interaction of such conductive layers and the RFsignal provided thereof be used to generate tissue heating at an edge ora tip of the insertion apparatus/device. For example, the firstelectrically conductive layer can include an inner electrode (which canbe or include, e.g., a device body, a conductive body, conductivecoating) and the second electrically conductive layer can include anouter electrode (which can be or include, e.g., an outer conductivecoating, a conductive body, etc.). The tissue being impacted using theRF signal can be based on the tissue detection determination performedusing the first electrically conductive layer and the secondelectrically conductive layer.

In another exemplary aspect of the present disclosure, the insertionapparatus/device can include a needle device, a cannula and/or otherinsertion configuration which has the first electrically conductivelayer, the lumen, the insulating layer and the second electricallyconductive layer.

According to still another exemplary embodiment of the presentdisclosure, an exemplary insertion apparatus/device can be providedwhich includes, for example, a hub and a shaft extending from the huband surrounding a lumen, where the shaft can include an outer surfacehaving an electrode(s) formed thereon or therein. A barrel can beconnected to the hub and a plunger can be configured to be inserted intothe barrel. A communication device(s) can be embedded in at least one of(i) the hub, (ii) the barrel, or (iii) a separate package which ismechanically and electrically connected to the hub or barrel. Theelectrode(s) can be configured to obtain an electrical signal, and ahardware processing arrangement can be embedded in (i) the hub, (ii) thebarrel, or (iii) a separate package which is mechanically andelectrically connected to the hub or barrel, where the hardwareprocessing arrangement can be configured to receive information relatedto the electrical signal, determine an impedance based on theinformation, and determine a tissue type based on the impedance. Theshaft can includes an insulating layer at least partially (e.g.,circumferentially) surrounded by the outer surface and an electricallyconductive layer at least partially (e.g., circumferentially) surroundedby the insulating layer, where the electrically conductive layer canform a further electrode. The electrode(s) can be integrated into theshaft.

Further, an exemplary insertion apparatus/device can include, forexample, a hub and a shaft surrounding a lumen, where the shaft caninclude at least two non-removable electrodes. A processing arrangementcan be configured to receive information related to (i) a firstelectrical signal obtained using a first one of the at least twonon-removable electrodes and (ii) a second electrical signal obtainedusing a second one of the at least two non-removable electrodes,determine an impedance based on the information, and determine a tissuetype based on the impedance.

According to still another exemplary aspect of the present disclosure,the insertion apparatus/device can include a needle device, a cannulaand/or other insertion configuration which include(s) the hub and thebarrel.

An exemplary method of determining a type of a tissue(s) of a subject(s)using an insertion apparatus/device can be provided. For example,according to such exemplary method, it is possible to, for example,receive a first electrical signal using a first electrically conductivelayer that at least partially (e.g. circumferentially) surrounds a lumenof the needle, receive a second electrical signal using a secondelectrically conductive layer that at least partially (e.g.circumferentially) surrounds the first electrically conductive layer,determine an impedance based on the first and second electrical signals,and determine the type based on the impedance, e.g., by comparing amagnitude of the impedance or a phase of the impedance withpredetermined values at one or more frequencies. The first electricallyconductive layer can be isolated from the second electrically conductivelayer using an insulating layer(s). Substances or materials into a bodyand/or an aspiration of fluids from the body, such as, e.g.,pharmacological agents, biologics, fillers, therapeutics, cellularmaterials, stem cells, genetic materials, immunotherapy agents, etc. canbe administered to the subject(s) through the lumen or a biopsy sampleand/or any other substance of fluid can be obtained or removed from thesubject(s) through the lumen.

Additionally, an exemplary method for determining a type of a tissue(s)of a subject(s) using an insertion device/apparatus can be provided.With such exemplary method, it is possible to, for example, receive anelectrical signal(s) using an electrode(s) formed on or in an outersurface of a shaft of the insertion device/apparatus, determine animpedance based on the at least one electrical signal, and determine thetype based on the impedance by comparing a magnitude of the impedance ora phase of the impedance with predetermined values at one or morefrequencies. Substances or materials, such as pharmacological agents,biologics, fillers, therapeutics, cellular materials, stem cells,genetic materials, immunotherapy agents, substances, etc. can beadministered to the subject(s) through the lumen of the insertiondevice/apparatus when a particular type is determined as being reachedby a particular portion of the insertion device/apparatus or a biopsysample can be obtained from the subject(s) through the lumen based onthe determination. Alternatively and/or in addition, it is possible toaspirate fluid or other material from the sample using the determinationof the type of the tissue reached by a particular portion of theinsertion device/apparatus.

Further, an exemplary method of determining a type of a tissue(s) of asubject(s) using an insertion device/apparatus can be provided. Withsuch exemplary method, it is possible to, for example, receive at leasttwo electrical signals using at least two non-removable electrodesintegrated into the insertion device/apparatus, determine an impedancebased on the at least two electrical signals, and determine the typebased on the impedance by comparing a magnitude of the impedance or aphase of the impedance with predetermined values at one or morefrequencies. Substances or materials, such as, e.g., pharmacologicalagents, fillers, biologics, therapeutics, cellular materials, stemcells, genetic materials, immunotherapy agents, etc. can be administeredto the subject(s) through the lumen of the insertion device/apparatuswhen a particular type is determined as being reached by a particularportion of the insertion device/apparatus or a biopsy sample can beobtained from the subject(s) through the lumen based on suchdetermination. Alternatively and/or in addition, it is possible toaspirate fluid or other material from the sample using the determinationof the type of the tissue reached by a particular portion of theinsertion device/apparatus.

An exemplary tissue and/or fluid detection apparatus can include, forexample, an insertion device/apparatus (e.g., which can be a needledevice, a cannula and/or other insertion configuration) that can beconfigured inject substances or materials, such as, e.g.,pharmacological agents, biologics, fillers, therapeutics, cellularmaterials, stem cells, genetic materials, immunotherapy agents,substances, etc. into a subject and/or remove a biopsy sample and/orother fluid, tissue, cells or material from the subject. The needle canbe used to receive one or more electrical signals, which can be used todetermine an impedance. The exemplary insertion device/apparatus caninclude a first electrically conductive layer at least partially (e.g.circumferentially) surrounding a lumen, an insulating layer at leastpartially (e.g. circumferentially) surrounding the first electricallyconductive layer, and a second electrically conductive layer at leastpartially (e.g. circumferentially) surrounding the insulating layer,where the insulating layer can electrically isolate the firstelectrically conductive layer from the second electrically conductivelayer. A further insulating layer can be included which can at leastpartially (e.g. circumferentially) surrounding the second electricallyconductive layer.

In some exemplary embodiments of the present disclosure, the exemplaryinsertion device/apparatus can include a hub and a shaft extending fromthe hub and surrounding a lumen, where the shaft can include an outersurface having an electrode(s) formed thereon or therein. In certainexemplary embodiments of the present disclosure, the exemplary needlecan include a hub and a shaft surrounding a lumen, where the shaft caninclude at least two non-removable electrodes. A communication devicecan be used to transfer/transmit information (e.g., wired or wirelessly)related to the electrical signals to a computer processing device. Theprocessing device, which can be a mobile apparatus (e.g., phone, tablet,etc.), can be used to determine the impedance based on the electricalsignals, and can also sense changes in the tissues and/or determine atissue or fluid type based on the impedance.

According to yet another exemplary embodiment of the present disclosure,the computer processing device can transmit RF signals via the exemplaryinsertion device/apparatus heat a tissue at or near the tip of theexemplary insertion device/apparatus by applying RF signals across theexemplary electrodes (e.g., inner electrode and an out electrode whichis insulated from the inner electrode), which can be done based on adetermination of the tissue characteristics at or near the tip of theinsertion device/apparatus. According to another exemplary embodiment ofthe present disclosure, the exemplary computer processing device canalso determine the position of a tip of the exemplary insertion devicein a three-dimensional space, e.g., using information provided by one ormore electronic probes (e.g., antennas) which facilitate, e.g., atriangulation and/or other position determination of the tip of theexemplary insertion device/apparatus based on a time of arrival of thesignals to the probes and/or strength of the signals received thereby.The determination of the location of the tip of the exemplary insertiondevice/apparatus can also be used to apply the RF signals across theelectrodes, e.g., when reaching a particular location within the subjecttissue.

As described above, the exemplary tissue detection, energy applicationand/or position indication system/apparatus can include a singleinsertion device/apparatus (e.g., needle, cannula, etc.). However, theexemplary tissue detection, energy application and/or positionindication system/apparatus can include a plurality of suchdevices/apparatuses (e.g., needles, cannula, etc., and/or anycombination thereof). Each tissue detection system/apparatus in thearray thereof s can have, the same or similar electrode design/structure(e.g., same or similar design of the various exemplary electrodedesigns/structures described herein). Alternatively or in addition, eachtissue detection, energy application and/or position indicationsystem/apparatus in the array can have a different design/structure, ora subset of the needles can have one design/structure while anothersubset can have a different design/structure. Each tissue detection,energy application and/or position indication system/apparatus in theexemplary array of needles can perform the exemplary tissue detection asdescribed herein, and each tissue detection system/apparatus can alsoperform a further function of, e.g., the administering of substances ormaterials, such as, e.g., pharmacological agents, biologics, fillers,therapeutics, cellular materials, stem cells, genetic materials,immunotherapy agents, etc. to the subject and/or the removal of a biopsysample and/or other materials or fluid from the subject (all at thespecific tissue based on the determination of a particular tissue of thesubject. Thus, one or more of such insertion devices in the exemplaryarray thereof can perform the tissue detection, while one or more otherneedles can perform the injection or aspiration functions. In accordancewith another exemplary embodiment of the present disclosure, theexemplary system/apparatus can utilize the same electrodes used fortissue detection (e.g., electrically conductive layers separated fromanother by an insulating layer, separate electrodes provided on thesurface of the insertion device/apparatus, etc.) to ablate the tissueunder review using RF signals applied to such electrodes, and athree-dimensional position/location of such tissue is based on thetissue detection determination which is performed using the same (ordifferent) electrodes.

The exemplary array of the insertion devices can also be used toincrease the accuracy of the tissue detection, tissue ablation and/orposition indication by increasing the number of the electrodes that areused to determine the impedance. Additionally or alternatively, acomparison of the impedance between insertion devices in the array canalso be used to determine the tissue type. According to anotherexemplary embodiment of the present disclosure, a method can be providedfor determining a type of at least one tissue of at least one subject orif an orifice of the tissue has been reached using an insertionarrangement (e.g., a needle arrangement). For example, it is possible to(i) insert the insertion arrangement into at least one portion of thesubject to reach the tissue; (ii) receive a first electrical signalusing a first electrically conductive layer that at least partiallysurrounds (e.g., circumferentially) a lumen of the insertionarrangement; (iii) receive a second electrical signal using a secondelectrically conductive layer that at least partially surrounds (e.g.,circumferentially) the first electrically conductive layer; (iv)determine an impedance based on the first and second electrical signals;and (v) determine whether the type or the orifice of the at least onetissue has been reached based on the impedance by comparing at least oneof a magnitude of the impedance or a phase of the impedance withpredetermined values at one or more frequencies. It is also possible toelectrically isolate the first electrically conductive layer from thesecond electrically conductive layer using at least one insulatinglayer. Further, it is possible to (i) administer a pharmacological agentto the subject through the lumen, and/or (ii) obtain a biopsy samplefrom the at least one subject through the lumen.

According to another exemplary embodiment of the present disclosure asimilar method can be provided for determining a type of at least onetissue of at least one subject or if an orifice of the tissue has beenreached using an insertion arrangement. For example, it is possible to(i) insert the insertion arrangement into at least one portion of the atleast one subject to reach the tissue; (ii) receive at least oneelectrical signal using at least one electrode formed on or in an outersurface of a shaft of the insertion arrangement; (iii) determine animpedance based on the at least one electrical signal; and (iv)determine whether the type or the orifice of the at least one tissue hasbeen reached based on the impedance by comparing at least one of amagnitude of the impedance or a phase of the impedance withpredetermined values at one or more frequencies. It is further possibleto (i) administer a substance, material or pharmacological agent to theat least one subject through a lumen of the needle or cannula, and/or(ii) obtain a biopsy sample from the at least one subject through thelumen.

According to a still exemplary embodiment of the present disclosure, amethod can be provided for determining a type of at least one tissue ofat least one subject or if an orifice of the tissue has been reachedusing an insertion arrangement (e.g., a needle arrangement). With theexemplary method, it is possible to (i) insert the insertion arrangementinto at least one portion of the subject to reach the tissue; (ii)receive at least one electrical signal (e.g., and possible at least twoelectrical signals) using at least two non-removable electrodesintegrated into the insertion arrangement; (iii) determine an impedancebased on the electrical signal(s); and (iv) determining whether the typeor the orifice of the tissue has been reached based on the impedance bycomparing at least one of a magnitude or a phase of the impedance withat least one predetermined value of at least one frequency. Similarly tothe previously-described exemplary embodiments, it is further possibleto (i) administer a pharmacological agent to the subject through a lumenof the insertion arrangement, and/or (ii) obtain a biopsy sample fromthe subject through the lumen.

All of the above-described exemplary embodiments can be utilized to,e.g., (i) deliver a composition into the tissue of the subject or anorifice of the tissue, and/or (ii) extract material or a fluid from atleast one tissue of at least one subject or an orifice of the at leastone tissue using an insertion device, e.g., at a particular location ofthe tissue corresponding a type of the tissue.

Further, an exemplary insertion apparatus/device according to anexemplary embodiment of the present disclosure can include, a basestructure comprising at least one lumen (or a plurality of lumens)extending along a length thereof, and at least oneoptically-transmissive layer circumferentially surrounding the basestructure and provided at least at a distal end of the base structure.For example, in operation, the optically-transmissive layer can beconfigured to transmit a particular optical radiation at the distal endthereof toward a target tissue.

Further, a cladding layer can be included which can at least partially(e.g. circumferentially) surrounding the second electrically conductivelayer. The first electrically conductive layer, the insulating layer,and the second electrically conductive layer can form a structure whichhas a first side and a second side disposed opposite to the first sidewith respect to the lumen, where the first side can be longer than thesecond side thereby forming a sharp pointed end via the first side at adistal-most portion of the insertion apparatus/device. The firstelectrically conductive layer, the insulating layer, and the secondelectrically conductive layer can form a structure that can be beveledto form a sharp pointed end at a distal-most portion of the insertionapparatus/device provided between the optically-transmissive layer andthe base structure. The cladding layer can have an optical index that isdifferent from an optical index of the optically-transmissive layer.Further, the optically-transmissive layer can be configured to transmitthe optical radiation in a first direction, and the cladding layer canbe configured to transmit a further optical radiation in a seconddirection which is opposite to the first direction.

According to another exemplary embodiment of the present disclosure, thecladding layer can be configured to transmit a further optical radiationfrom the tissue, and the further optical radiation can be based on theparticular optical radiation.

In another exemplary embodiment of the present disclosure, a furthercladding layer can be provided that circumferentially surrounds theoptically-transmissive layer. At least one furtheroptically-transmissive layer can be include that circumferentiallysurrounds the further cladding layer. The optically-transmissive layerand the further optically-transmissive layer can be configured totransmit the particular optical radiation in a first direction, and thecladding layer and the further cladding layer can be configured totransmit a further optical radiation in a second direction which isopposite to the first direction. The cladding layer and the furthercladding layer can be configured to transmit the further opticalradiation from the tissue, and the further optical radiation can bebased on the particular optical radiation.

According to a further exemplary embodiment of the present disclosure,the optically-transmissive layer can include a plurality of coresections which are optically separated from one another. For example,one of the core sections can be configured to transceive at least onefirst portion of the particular optical radiation, and another one ofthe core sections can be configured to transceive at least one secondportion of the particular optical radiation. The first and secondportions can be optically separated from one another. A cladding layercan be provided between the optically-transmissive layer and the basestructure. For example, one of the core sections can be optically andphysically separated from another one of the core sections by at leastone cladding section of the cladding layer. At least one of the coresections can be configured to transceive at least one first portion ofthe particular optical radiation at least one first portion of theparticular optical radiation, and the cladding section can be configuredto transceive at least one second portion of the particular opticalradiation. The first and second portions can be optically separated fromone another.

In yet another exemplary embodiment of the present disclosure, anoptical multiplexer can be provided that is configured to multiplex theparticular optical radiation provided to the tissue and a return opticalradiation provided from the tissue which is associated with theparticular optical radiation. A hardware processing arrangement can beprovided which can be configured to (i) receive information related tothe return optical radiation, and (ii) determine data, based on theinformation. Such data can be, e.g., (i) at least one characteristic ofthe tissue, (ii) at least one location of a target area of the tissue,and/or (iii) a location of a tip of the base structure with respect tothe tissue. At least one audible arrangement can be provided which isconfigured to emit a sound based on the data. Alternatively or inaddition, it is possible to provide a visual indicator (e.g., LED, lamp,display, etc.) to generate an image or provide information based on thedata.

According to a further exemplary embodiment of the present disclosure,the base structure can include at least one lumen extending therethrough that is configured to have a pharmacological agent injectedthere through. Examples include can photosentizers, such as, e.g.,porfimer sodium which can be delivered locally through the lumen andthen activated with light delivered through the optically transmissivelayer. This can minimize exposure of tissues other than those targetedby the photodynamic therapy. Potential applications include oncology andimproved implant patency. Alternatively or additionally, the at leastone lumen can be used have a biopsy sample obtained there through. Theoptically-transmissive layer can includes at least one helical-patternedstructure which define an outer patterned section of the insertionapparatus. A computer hardware arrangement can be provided which can beconfigured to determine a three-dimensional location of at least oneportion of the insertion apparatus based on information received by thecomputer hardware arrangement from the optically-transmissive layerwhich is associated with a return optical radiation provided from thetissue which is based on a particular optical radiation. In anotherexemplary embodiment of the present disclosure, a method can be providedfor determining information associated with at least one tissue of atleast one patient or if an orifice of the at least one tissue has beenreached using an insertion apparatus/arrangement. Using such exemplarymethod, it is possible to (i) insert the insertion apparatus/arrangementinto at least one portion of the patient to reach the tissue, (ii)transmit a first optical radiation using (a) at least oneoptically-transmissive layer that circumferentially surrounds a basestructure or a cladding layer, or (b) the cladding layer, (iii) receivea second optical radiation via at least another one of (a) theoptically-transmissive layer, and/or (b) the cladding layer based on thefirst optical radiation, and determining data, based on the secondoptical radiation, which can be (a) at least one characteristic of thetissue, (b) at least one location of a target area of the tissue, and/or(iii) a location of a tip of the base structure with respect to thetissue.

For example, it is also possible, to (i) administer a pharmacologicalagent to the patient through a lumen of the base structure, and/or (ii)obtaining a biopsy sample from the patient through the lumen. It isfurther possible to, based on the data, ablate an area of the at leastone tissue by applying a further optical radiation to the tissue, whichcan utilize, e.g., a Photodynamic Therapy (PDT). It is yet furtherpossible to determine a three-dimensional location of at least oneportion of the insertion apparatus at or in a body based on the data. Itis additionally possible to generate an image on a display of at leastone portion of the insertion apparatus at or in a body in athree-dimensional space based on the data.

In another exemplary embodiment, the structure such as, e.g., a catheteror needle can be used to reduce and/or stop blood flow or stabilizeabnormal tissues such as, e.g., fibroids, tumors, and aneurisms throughphotopolymerization. The structure can, e.g., a) be guided through ablood vessel to the target area such as a uterine fibroid, b) deliver amonomer such as poly(ethylene glycol) diacrylate mixed with aphotoinitiator such as1-[4-(2-hydroxyethoxy)-phenyl]-2-hydroxy-2-methyl-1-propane-1-one(α-HAP) through one or more lumens, and then c) cross-link the materialin-situ by exposing the material to UV-A light delivered through theoptically transmissive layer.

According to a further exemplary embodiment of the present disclosure,an insertion apparatus can be provided with, e.g., a hub and a shaftextending from the hub and surrounding a lumen. The shaft can include anouter surface having at least one electrode formed thereon or therein,and the electrode(s) extends for more than half of an externalcircumference of the shaft. The insertion apparatus can also include,e.g., a barrel connected to the hub, and a plunger configured to beinserted into the barrel.

In another exemplary embodiment of the present disclosure, a method canbe provided for determining information regarding at least one tissue ofa subject or an orifice of the at least one tissue using an insertionarrangement. The exemplary method can comprise, e.g., introducing theinsertion arrangement into at least one target site of the subject toreach the at least one tissue, transmitting an electrical signal using afirst electrically conductive layer that at least partially surrounds alumen of the insertion arrangement, receiving the electrical signalusing a second electrically conductive layer that at least partiallysurrounds the first electrically conductive layer, and determining animpedance based on the electrical signal, thereby determining theinformation regarding the tissue or the orifice of the one tissue of thesubject. It is also possible to isolate the first electricallyconductive layer from the second electrically conductive layer using atleast one insulating layer. A value of the impedance can be themagnitude of the impedance. The tissue can be muscle or fat. The orificecontains blood, epidural fluid or synovial fluid. It is also possible todetermine whether a particular type or an orifice of at least one tissuehas been reached based on the impedance. Further based on thedetermination of whether the type or the orifice of the at least onetissue has been reached, it is possible to provide at least one currentto at least one of the first electrically conductive layer or the secondelectrically conductive layer so as to generate an energy fielddetectable by signals detectors which transmit location information atleast one portion of the insertion apparatus to a computer hardwarearrangement. It is additionally possible to determine athree-dimensional location of the at least one portion of the insertionapparatus at or in a body based on the location information. An imagecan be generated on a display of the at least one portion of theinsertion apparatus at or in a body in a three-dimensional space basedon the location information.

According to another exemplary embodiment of the present disclosure, amethod can be provided to determine a type of at least one tissue of atleast one subject or if an orifice of the tissue has been reached usingan insertion arrangement a spinal cord or a joint of at least onepatient. The exemplary method can include, e.g., inserting the insertionarrangement into at least one portion of the at least one subject toreach the at least one tissue, receiving at least one electrical signalusing at least one electrode formed on or in an outer surface of a shaftof the insertion arrangement, and determining an impedance based on theat least one electrical signal at one or more frequencies, therebydetermining the type or whether the orifice of the tissue has beenreached.

In still another exemplary embodiment, a method can be provided fordetermining a type of at least one tissue of at least one subject or ifan orifice of the tissue has been reached using an insertion arrangementin a tumor tissue determination. The exemplary method can include, e.g.,inserting the insertion arrangement into at least one portion of the atleast one subject to reach the tissue, receiving at least one electricalsignal using at least two non-removable electrodes integrated into theinsertion arrangement, and determining an impedance based on the atleast one electrical signal for at least one frequency, therebydetermining the type tissue of at least one subject or whether theorifice of the tissue has been reached using an insertion arrangement ina tumor tissue determination. The electrical signal can include at leasttwo electrical signals, and the impedance can be determined based on theelectrical signals.

Further, an insertion apparatus can be provided for determining a typeof tissue in a spinal cord or a joint of at least one patient. Theapparatus can comprise, e.g., a first electrically conductive layercircumferentially surrounding a lumen, an insulating layer at leastpartially surrounding the first electrically conductive layer, and asecond electrically conductive layer at least partially surrounding theinsulating layer. The insulating layer can electrically isolate thefirst electrically conductive layer from the second electricallyconductive layer.

According to the exemplary embodiment of the present disclosure, the useof the exemplary system, method and computer-accessible medium of thepresent disclosure which provide a precise and targeted control ofbipolar energy application with respect to tissue damage can facilitatean application of tissue ablation sensitive areas, such as, e.g., thebrain or spine (via, e.g., tumor ablation) as the zone of damage thereinor thereon should be limited to avoid un wanted damage and effects.

According to the exemplary embodiment of the present disclosure, anexemplary configuration of concentric electrodes can provide acontinuous ring of ablation. For biopsy applications, when applying RFenergy across the exemplary concentric electrodes, such energy cancoagulate tissue to reduce and/or prevent bleeding while cutting throughtissue. Since the cutting of the tissue can be performed using anelectrical current, the sharpness of the instrument is also lessimportant for a cutting performance. Conventional biopsy instrumentstypically have a sharp cutting edge which needs to be grinded or cut,then dulls with use. However, in one non-limiting example, the exemplaryconcentric electrode configuration can be provided on or in a simplebiopsy instrument, for example, a punch, as a cost-effective option viaa coated tubing.

An exemplary insertion device/instrument according to various exemplaryembodiments of the present disclosure, which can include, but notlimited to, e.g., a biopsy needle, can also be composed of and/orinclude a coated tubing. It is possible to make end thereof sharp invarious way (including but not limited to grinding the edge) to a pointso as to pierce or otherwise enter tissue through skin, and facilitate apassage of the tip to a target location, which can be identified usingthe tissue type determination. Indeed, e.g., the electrodes of theexemplary device/apparatus can provide/facilitate a determination ofvariations in tissue type(s), and actively cut, ablate and/or remove atissue sample based on such determination.

Turning to the exemplary embodiment of the present disclosure whichutilizes the alternating current via the electrodes that are separatedby an insulating layer (e.g., which can be and/or include concentricelectrodes and/or coatings) to obtain a three-dimensional position ofthe tip of the exemplary insertion device/apparatus, such position canbe, e.g., real-time three-dimensional (3D) absolute position of the tip(which is certainly more beneficial than the two-dimensional positionwhich can be obtained using an ultrasound modality). As an additionalbenefit, either very little or no radiation exposure is encountered bypatient or clinician associated with an X-ray or CT scan which can beused to implement this exemplary embodiment of the present disclosure.If certain equipment is used to guide the exemplary insertiondevice/apparatus that is under MRI guidance, such equipment can be MRIcompatible, and thereby reducing the need to provide extensivedevelopment of devices.

According to still another exemplary embodiment of the presentdisclosure, method and procedure for providing an insertion arrangementfor an anatomical structure can be achieved. For example, it is possibleto provide a tubular arrangement configured for the insertion into atleast one portion of the anatomical structure. It is then possible tospray a first electrically conductive coating onto a surface of thetubular arrangement to provide a first electrically conductive layer. Anelectrical insulating mixture sputter-coating on the first electricallyconductive layer to produce an electrically-insulating layer. A secondelectrically conductive coating can be dip-coated onto an externalportion of the electrically-insulating layer to provide a secondelectrically conductive layer. The first conductive layer, theelectrically-insulating layer and the second electrically conductinglayer can form a concentric electrode configuration.

These and other objects, features and advantages of the exemplaryembodiments of the present disclosure will become apparent upon readingthe following detailed description of the exemplary embodiments of thepresent disclosure, when taken in conjunction with the appended claims.

BRIEF DESCRIPTION OF THE DRAWINGS

Further objects, features and advantages of the present disclosure willbecome apparent from the following detailed description taken inconjunction with the accompanying Figures showing illustrativeembodiments of the present disclosure, in which:

FIG. 1A is an exemplary diagram of a close-up cross-sectional view of adistal end of an exemplary insertion device/apparatus (e.g., a needle)which illustrates the ability of the device/apparatus to sense at theleading edge or tip according to an exemplary embodiment of the presentdisclosure;

FIG. 1B are a set of exemplary diagrams of cut-away view and a close-upcross-sectional view of a distal end of an exemplary insertiondevice/apparatus according to another exemplary embodiment of thepresent disclosure;

FIG. 1C is a top view of an exemplary application of the exemplaryinsertion device/apparatus provided on a body according to yet anotherexemplary embodiment of the present disclosure;

FIG. 1D is an exemplary diagram of a close-up cross-sectional view of adistal end of an exemplary insertion device/apparatus (e.g., needle,endoscope, cannula, etc.) according to an exemplary embodiment of thepresent disclosure which includes an optically-transmissive coatingprovided on a surface a base structure of the exemplary insertiondevice/apparatus;

FIG. 1E a close-up perspective view of a distal end of the exemplaryinsertion device/apparatus according to another exemplary embodiment ofthe present disclosure shown in FIG. 1D;

FIG. 1F is a set of exemplary diagrams of a close-up cross-sectionalview, as well as cut-away side views of a distal end of an exemplaryinsertion device/apparatus that includes a configuration that providesand/or detects mechanical vibrations thereof according to an exemplaryembodiment of the present disclosure;

FIG. 1G is an exemplary diagram of a side view of a surgical instrumentthat includes the exemplary insertion device/apparatus, and which cangenerate and/or detect mechanical vibrations for possible cutting and/orclamping tissue of interest according to an exemplary embodiment of thepresent disclosure;

FIG. 2A is a further exemplary diagram of an elevation view of thedistal end of the exemplary insertion device/apparatus according to anexemplary embodiment of the present disclosure;

FIG. 2B is a set of exemplary diagrams of a close-up perspective viewand a cross-sectional view, of an exemplary insertion device/apparatusthat includes a configuration that includes a cladding layer therein,according to another exemplary embodiment of the present disclosure;

FIG. 2C is another exemplary diagram of front and perspective views ofan exemplary insertion device/apparatus according to still anotherexemplary embodiment of the present disclosure in which theoptically-transmissive coating is provided as multiple section separatedfrom one another;

FIG. 2D is an exemplary diagram of front and perspective views of anexemplary insertion device/apparatus according to still anotherexemplary embodiment of the present disclosure in which multiple sectionof the optically-transmissive layer are provided on the cladding layer,and are separated from one another via sections of the cladding later;

FIG. 3 is an exemplary diagram of various exemplary steps/procedures ofa method for applying layers to the exemplary insertion device/apparatusaccording to an exemplary embodiment of the present disclosure;

FIG. 4A is an exemplary image of the exemplary insertiondevice/apparatus according to an exemplary embodiment of the presentdisclosure;

FIG. 4B is an exemplary close-up image illustrating the structure of theexemplary insertion device/apparatus fabricated with a layer ofpolyimide and an outer layer of silver conductive ink applied using aspray process according to an exemplary embodiment of the presentdisclosure;

FIG. 5 is an exemplary image of exemplary insertion devices/apparatusesproduced using a grinding process according to an exemplary embodimentof the present disclosure;

FIG. 6 is a set of side views of exemplary diagrams of differentconductive traces used for the exemplary insertion device/apparatusaccording to an exemplary embodiment of the present disclosure;

FIG. 7 is an exemplary image of an exemplary insertion device/apparatushaving a surface electrode that was pad printed using ink according toan exemplary embodiment of the present disclosure;

FIG. 8 is an exemplary expanded diagram of the distal end of theexemplary insertion device/apparatus having electrodes patterned on theexemplary insertion device/apparatus according to an exemplaryembodiment of the present disclosure;

FIG. 9A is a side view of the exemplary insertion device/apparatusaccording to an exemplary embodiment of the present disclosure;

FIG. 9B is a perspective view of the exemplary insertiondevice/apparatus according to another exemplary embodiment of thepresent disclosure;

FIG. 9C is a side view of the exemplary insertion device/apparatus shownin FIG. 9B with the tip thereof extending in a downward direction;

FIG. 9D is a cross-sectional exploded side view of an electricalconnection section of the exemplary insertion device/apparatus shown inFIGS. 9B and 9C;

FIG. 9E is a side image of the exemplary insertion device/apparatus ofFIGS. 9B-9D connected to a cable;

FIG. 10A is an exemplary image of the exemplary insertiondevice/apparatus having magnetic wires attached thereto according to anexemplary embodiment of the present disclosure;

FIG. 10B is an exemplary diagram of the exemplary insertiondevice/apparatus shown in FIG. 10A illustrating the attachment of themagnetic wire according to an exemplary embodiment of the presentdisclosure;

FIG. 10C is an exemplary graph showing impedance versus frequency forvarious tissue types according to an exemplary embodiment of the presentdisclosure;

FIG. 11 is a set of side cross-sectional views of another exemplaryembodiment of the exemplary insertion apparatus which provides anexemplary sensing technology implemented in the form of a cannula,according to yet another exemplary embodiment of the present disclosure;

FIG. 12A is a set of exemplary illustrations showing the exemplaryinsertion device/apparatus inserted into different tissue typesaccording to an exemplary embodiment of the present disclosure;

FIG. 12B is a set of exemplary graphs illustrating the impedance phaseangle obtained as a function of frequency with the tip of the insertiondevice/apparatus inserted into different types of tissues according toan exemplary embodiment of the present disclosure;

FIG. 13 is an exemplary diagram illustrating wireless transmission ofinformation from the exemplary insertion device/apparatus for use indetermining the tissue type according to an exemplary embodiment of thepresent disclosure;

FIG. 14 is an exemplary diagram of an exemplary mobile device used toreceive the wireless transmission of information from the exemplaryinsertion device/apparatus shown in FIG. 13, which can be used todetermine the tissue type according to an exemplary embodiment of thepresent disclosure;

FIGS. 15-18C are exemplary graphs showing exemplary results obtainedusing the exemplary insertion device/apparatus according to an exemplaryembodiment of the present disclosure;

FIGS. 19A-19D are exemplary flow diagrams of exemplary methods ofdetermining a type of a tissue of a subject using the exemplaryinsertion device/apparatus;

FIGS. 20A and 20B are illustration of an exemplary treatment ofedematous fibrosclerotic panniculopathy (EFP), commonly known ascellulite, through the injection of a particular substance in accordancewith the exemplary embodiment of the present disclosure;

FIG. 20C is an illustration of an exemplary procedure involving a spinalinjection performed to diagnose and/or alleviate the source of pain ordiscomfort, in accordance with the exemplary embodiment of the presentdisclosure;

FIG. 20D is an illustration of an exemplary procedure involving aninjection of substances (e.g., such as platelet rich plasma (PRP) orhyaluronic acid (HA)) into the synovial space in accordance with theexemplary embodiment of the present disclosure;

FIG. 21A is an illustration of an exemplary block diagram of anexemplary system in accordance with certain exemplary embodiments of thepresent disclosure;

FIG. 21B is an illustration of an exemplary device incorporating theexemplary insertion apparatus tethered to an external electronicspackage to infer impedance along with a data device connected wirelesslyvia Bluetooth to a data device which displays and records data,according to an exemplary embodiment of the present disclosure;

FIG. 21C is an illustration of exemplary data collected during needleinsertion into a rabbit femoral vein using a device with externalelectronics, according to an exemplary embodiment of the presentdisclosure;

FIG. 21D is an illustration of the operation of an exemplary integratedsystem using lights to provide information to a user, according to anexemplary embodiment of the present disclosure;

FIG. 22A is an exemplary diagram of an exemplary device for use in corebiopsies, according to an exemplary embodiment of the presentdisclosure;

FIG. 22B is an exemplary diagram of the cross-section of the exemplarydevice shown in FIG. 22A, according to an exemplary embodiment of thepresent disclosure;

FIG. 22C is an exemplary diagram of the exemplary device shown in FIG.22A inserted into a breast, according to an exemplary embodiment of thepresent disclosure;

FIG. 22D is an exemplary image of the exemplary device shown in FIG. 22Ainserted into a mouse and a set of exemplary graphs illustrating theresulting measurements, according to an exemplary embodiment of thepresent disclosure;

FIG. 23A is an exemplary image showing the exemplary device beinginserted into a joint, according to an exemplary embodiment of thepresent disclosure;

FIG. 23B is an exemplary diagram of a joint, according to an exemplaryembodiment of the present disclosure; and

FIG. 23C is a set of exemplary graphs illustrating real-time feedbackfor two trials, according to an exemplary embodiment of the presentdisclosure.

Throughout the drawings, the same reference numerals and characters,unless otherwise stated, are used to denote like features, elements,components or portions of the illustrated embodiments. Moreover, whilethe present disclosure will now be described in detail with reference tothe figures, it is done so in connection with the illustrativeembodiments and is not limited by the particular embodiments illustratedin the figures and the appended claims.

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS

The exemplary embodiments of the present disclosure may be furtherunderstood with reference to the following description and the relatedappended drawings. In particular, the exemplary embodiments of thepresent disclosure relate to at least one insertion device/apparatus(which can be an array thereof) for use in determining a tissue or fluidtype. Such determination can be made prior to the injection of a drug.Tissue type can include, but is not limited to, dermis, fat, muscle,skin, bone, nerves, muscle, eye tissue, organ tissue, teeth, etc. Fluidsinclude blood, synovial fluid, lymph fluid, etc. The exemplaryembodiments are described with reference to an exemplary insertiondevice/apparatus, it should be abundantly clear the exemplaryembodiments of the present disclosure may be implemented on otherinsertion and/or injection devices for use in injecting substances intothe body of a subject and/or removing substances and/or materialstherefrom, including but not limited cannulas, catheters, etc. As usedherein, the exemplary insertion device/apparatus can be used on a person(e.g., a human). However, the exemplary insertion device/apparatus canalso be used for other subjects including, but not limited to, animals,or other various species.

According to a further exemplary embodiment of the present disclosure,the exemplary insertion device/apparatus can be used to apply aradiofrequency (RF) signal to the tissue being inspected. Suchapplication of RF signals to specific tissues can be based on the tissuedetection determination performed using same components of the exemplaryinsertion device/apparatus used for the tissue detection. In still afurther exemplary embodiment of the present disclosure, the exemplaryinsertion device/apparatus can be used to determine or infer a positionof a tip thereof in three-dimensional space, e.g., using some of thesame components used for the used for the tissue detection and/or the RFsignal application.

It should also be understood that any reference to a needle, needleapparatus, etc. according to various exemplary embodiments of thepresent disclosure described herein also includes, and equallyapplicable to, other insertion devices for providing and/or extractingsubstances and/or materials to and from a body, including but notlimited to cannulas, endoscopes, laparoscopes, etc.

The exemplary apparatus can utilize, for example, electrical impedanceto selectively determine when at least one insertion device (e.g., aneedle) has been introduced into a specific type of tissue (such as ablood vessel—e.g., an artery or vein, or into a tissue such as, e.g.,fat). The exemplary apparatus can operate utilizing an alternatingvoltage applied to two or more electrodes located on the apparatus,which can be used to measure the resulting current. Such impedance canbe determined from, e.g., the ratio between the voltage and current, andcan be, e.g., a complex number (e.g., includes real and imaginarycomponents). The calculated electrical impedance can vary with thefrequency and the tissue type. Various exemplary characteristics of themeasured impedance (e.g., magnitude and angle as a function offrequency, etc.) can be used to determine tissue type. Suchdetermination can be performed using the exemplary system, device andcomputer-accessible medium with the use of a processor executing aprogram that can utilize the information/data associated with the ratioof the voltage, current, etc. as well as other values and information.

In one exemplary embodiment of the present disclosure, the exemplaryapparatus, devices and/or systems can be used to measure the impedanceat the tip of an insertion device/apparatus (such as, e.g., needle,cannula, endoscope, laparoscope, a hypodermic needle, etc.), and candetermine when the tip of the insertion device/apparatus is locatedwithin a specific type of tissue or orifice without any alteration tocurrent clinical practice. In this exemplary manner, a medicalprofessional can determine the location of the insertiondevice/apparatus (e.g., the tissue type) prior to injecting an agentinto the subject. Once the correct tissue type for depositing the agenthas been determined, the medical professional can introduce (e.g.,inject) the agent into the subject. No stylet or other component isneeded in order to determine the tissue type. Additionally, theexemplary apparatus can provide an audible, tactile and/or visual alertbased on the tissue type.

The exemplary apparatus can include, or can be connected to, forexample, a display screen which can intermittently or continuouslyprovide the medical professional or any person inserting the exemplaryinsertion device/apparatus the information regarding the determinedtissue or fluid type based on the determined electrical impedance. Forexample, when the medical professional first introduces the insertiondevice/apparatus into the subject, the display can indicate the firsttissue or fluid type the insertion device/apparatus is inserted into. Asthe medical professional pushes the insertion device/apparatus furtherinto the subject, the display device can change as the tissue or fluidtype changes. Such change can include providing different colors,shapes, visual indicators, etc. Once the correct or specific tissue orfluid type has been determined as being reached (e.g., based on a visualindication to the medical professional), the medical professional cancease pushing the insertion device/apparatus, and inject any material orsubstance into the subject at the location of the tip of the insertiondevice/apparatus, and/or extract any material or substance therefrom.Alternatively, or in addition, the exemplary apparatus can be programmedbased on a particular impedance value or tissue or fluid type (e.g., atissue or fluid type selected by the medical professional to inject theagent into), and an audible alert can sound once the exemplary apparatushas determined the selected impedance value or tissue or fluid type. Theaudible or light indicator alert can also be programmed to provide avariable tone or light to represent passage through various tissues orfluids, for example, with a frequency that varies with impedance.Through the present disclosure, the terms materials and/or substance areunderstood to include a pharmacological agent (e.g., a drug), biologics,fillers, therapeutics, cellular materials, stem cells, geneticmaterials, immunotherapy agents, etc., but certainly not limitedthereby.

For example, the exemplary apparatus, devices and systems can be usedfor immunotherapeutic applications including, but not limited to, thecontrolled subcutaneous delivery of allergens (e.g. food, mold, animal,dust mite and pollen allergens) to help reduce the allergic response ofa subject to such allergens. Food allergies are an increasing globalhealth concern and, in Europe alone, about 17 million people areaffected; 3.5 million of which are under the age of 25. Food allergiescan be life threatening resulting in over 300,000 ambulatory care visitsof people under the age of 18 and 150 deaths due to anaphylactic shockper year. Current methods of allergen-related immunotherapy utilize therepetitive subcutaneous injection of small doses of allergen into asubject. A serious risk in current methods of allergen-relatedimmunotherapy is accidental injection of the allergen dose into a bloodvessel resulting in the systemic dispersal of the allergen. Such asystemic dispersal can cause a severe allergic reaction in the subjectresulting in death from anaphylactic shock. By using the exemplaryapparatus, devices and systems, blood vessels can be readily and easilydetected and avoided, thereby decreasing or eliminating the risk ofaccidental injection of an allergen into a blood vessel.

In another exemplary embodiment of the present disclosure, the exemplaryapparatus can be connected to an RF source, such RF source can providethe RF signal to one of the same electrodes located on or in theapparatus. As the electrodes can be electrically insulated from oneanother, the RF signal's application to one of the electrodes can applythe RF signal across the electrodes, e.g., at a tip of the exemplaryapparatus—which can apply such RF signal across an inner electrode(which can be or include, e.g., a device body) and an outer electrode(which can be or include, e.g., outer conductive coating). For example,if it is determined that a certain tissue structure has been encounteredat the tip of the exemplary apparatus—using the electrodes as describedherein above—the exemplary apparatus can then be activated to ablate atleast a portion of such tissue by applying the RF signal across theelectrodes.

According to yet another exemplary embodiment of the present disclosure,the exemplary apparatus can use alternating current applied to theexemplary electrodes to determine and/or infer a three-dimensionalposition of the tip of the exemplary apparatus. Such information canalso be used for ablating the tissue and/or determining the type of thetissue under examination. For example, the alternating current canproduce an electromagnetic (EM) field at the tip of the exemplaryapparatus which can be detected using, e.g., one or more electromagneticprobes (antennas) placed on or near the surface of the body. Theexemplary probe(s) can facilitate, e.g., a triangulation of the positionof the tip of the exemplary apparatus from time of arrival and/or signalstrength data.

The exemplary apparatus, devices and systems can include a fully opencenter lumen, which can facilitate the insertion device/apparatus to beused to deliver any material, substance and/or agent, as well as for,collection, or introduction of other devices (e.g., medical devices)through the lumen. Thus, the exemplary apparatus, devices and systemscan be comparable to standard hypodermic needles which are generallycharacterized by their internal diameter. Further, the exemplaryinsertion device/apparatus can be fully integrated and tuned to sensespecific tissues. For example, a particular insertion device/apparatuscan be used for a particular tissue (e.g., the insertiondevice/apparatus can be tuned to specific frequencies to detect a singletype of tissue by reviewing the magnitude and/or phase components of theimpedance). The exemplary angle of the tip and/or the width of theinsertion apparatus/device described for the exemplary embodiments canbe provided and/or fabricated based on various different characteristicsof the tissue into which the exemplary insertion device/apparatus isinserted. With respect to the tissue type determination, this canfacilitate the electronics of the exemplary apparatus, devices andsystems to determine the impedance to be simplified since the exemplaryapparatus, devices and systems do not need to obtain a complete spectra,as the exemplary apparatus, devices and systems would only preferablyobtain the spectra for the particular tissue type. The exemplaryelectrodes can be applied using a spray or deposition process, asdiscussed below. The resulting structure can then be used to produce theexemplary insertion device using conventional grinding and insertiondevice/apparatus fabrication processes. Additionally, the innerelectrode can include the base body of the insertion device/apparatusitself. Two, three, or more electrodes can then be provided by applyingadditional layers to the insertion device/apparatus. As discussedherein, the exemplary angle of the tip and/or the width of the insertionapparatus/device described for the exemplary embodiments can be providedand/or fabricated based on various different characteristics of thetissue into which the exemplary insertion device/apparatus is inserted.

The exemplary apparatus can be used in the field of a filler injection,including but not limited to a facial filler injection, etc. Forexample, an injection of a filler into an artery can cause a partial ortotal vessel occlusion which can lead to tissue necrosis. (See e.g.,Reference 6). To address this problem, an exemplary insertion andguidance device/apparatus according to an exemplary embodiment of thepresent disclosure can provide feedback to a clinician or a medicalprofessional indicating that the tip or opening of such insertiondevice/apparatus is provided in a blood vessel. In this manner, themedical professional can avoid dispensing the filler into any bloodvessel, including, e.g., artery, vein, capillary, etc. Then, occlusionscreated by certain materials and/or substance (e.g., fillers) injectedinto a blood vessel (e.g., an artery, a vein, etc.) can be cleared. Suchmaterials and/or substances can include hyaluronic acid. Hyaluronidaseis an enzyme that can be used to dissolves hyaluronic acid. Occlusionsdetected in a timely manner can be cleared by injecting hyaluronidase.An exemplary perfusion detection apparatus can provide an alert thatthere is an occlusion such that action can be taken before extensivecell death occurs.

For example, the exemplary fillers can include, but certainly notlimited to, absorbable or temporary materials (e.g., Collagen,Hyaluronic acid, Calcium hydroxylapatite, Poly-L-lactic acid (PLLA)),non-absorbable or permanent materials (e.g., Polymethylmethacrylatebeads (PMMA microspheres)), as well as other materials. VariousFDA-approved fillers can be as follows: Restylane Lyft with Lidocaine,Revanesse Versa, Revanesse Versa+, Rha 2, Rha 3, Rha 4, Juvederm VollureXC, Restylane, Refyne, Restylane Defyne, Juvederm Volbella XC\,Radiesse, Restylane Silk, etc.

In another exemplary embodiment of the present disclosure at least oneinsertion device/apparatus (which can be an array thereof) can beprovided for use in delivering optical radiation to tissue anddetermining tissue characteristics and/or the effect of the opticalradiation delivery on the impacted tissue and/or surrounding areas. Theexemplary embodiments are described with reference to an exemplaryinsertion device/apparatus, and can include but not limited cannulas,catheters, laparoscopes, needles, etc. As used herein, the exemplaryinsertion device/apparatus can be used on a person (e.g., a human).However, the exemplary insertion device/apparatus can also be used forother subjects including, but not limited to, animals, or other variousspecies.

According to a further exemplary embodiment of the present disclosure,the exemplary insertion device/apparatus can be used to apply an opticalradiation (e.g., light, etc.) to the tissue that is of interest. Suchapplication of optical radiation to specific tissues can be based on atissue detection determination performed using same components of theexemplary insertion device/apparatus used for the radiation application.

In one exemplary embodiment of the present disclosure, the exemplaryapparatus, devices and/or systems can be used to transmit opticalradiation to the tissue at a tip of the insertion device/apparatus viaan optical coating located thereon, and then receive a returning opticalradiation from the tissue being impacted by such radiation to determineinformation regarding the tissue, e.g., at the tip of an insertiondevice/apparatus (such as, e.g., needle, cannula, endoscope,laparoscope, cannula, a hypodermic needle, etc.), and can determine whenthe tip of the insertion device/apparatus is located within a specifictype of tissue or orifice without any alteration to current clinicalpractice. In this exemplary manner, a medical professional can determinethe location of the insertion device/apparatus (e.g., the tissue type)prior to injecting an agent into the patient. Once the correct tissuetype or location of the tissue for depositing the agent has beendetermined, the medical professional can introduce (e.g., inject) theagent into the patient. No stylet or other component is needed in orderto determine the tissue type or location of the tissue. Additionally,the exemplary apparatus can provide an audible, tactile and/or visualalert based on the tissue type.

The exemplary apparatus can include, or can be connected to, forexample, a display screen which can intermittently or continuouslyprovide the medical professional or any person inserting the exemplaryinsertion device/apparatus the information regarding the determinedtissue (or fluid) type or location of the tissue based on theinformation provided by the return optical radiation provided from thetissue. For example, when the medical professional first introduces theinsertion device/apparatus into the patient, the display can indicatethe first tissue type or location of the tissue that the insertiondevice/apparatus is inserted into. As the medical professional providesthe insertion device/apparatus further into the patient, the displaydevice can change as the tissue or fluid type or location of the tissuechanges, e.g., providing information regarding the tissuecharacteristics at the tip of the insertion device/apparatus,illustrating the 360 degree view of the tissue at various locations inreal time, etc. Such change can also include providing different colors,shapes, visual indicators, fly-through, etc. In one example, once thespecific tissue-type or fluid-type or location of the tissue has beendetermined as being reached (e.g., based on a visual indication to themedical professional), the medical professional can cease pushing theinsertion device/apparatus, and inject any material or substance intothe patient at the location of the tip of the insertiondevice/apparatus, and/or extract any material or substance therefrom.Alternatively, or in addition, the exemplary apparatus can be programmedbased on a particular issue or fluid-type type or location of the tissue(e.g., a tissue or fluid-type and/or tissue location selected by themedical professional to inject the agent into), and an audible alert cansound once the exemplary apparatus has determined the selected tissueand/or fluid-type. The audible or light indicator alert can also beprogrammed to provide a variable tone and/or light to represent passagethrough various tissues or fluids, for example, with a frequency thatvaries with impedance. Through the present disclosure, the termsmaterials and/or substance are understood to include a pharmacologicalagent (e.g., a drug), fillers, therapeutics, cellular materials, stemcells, genetic materials, immunotherapy agents, etc., but certainly notlimited thereby.

According to yet another exemplary embodiment of the present disclosure,the exemplary apparatus can use the optical radiation returning from thetissue being impacted by the forwarded optical radiation to determineand/or infer a three-dimensional position of the tip of the exemplaryapparatus. Such information can also be used for delivering an agent fortreatment which is activated or otherwise effected by subsequentapplication of further optical radiation.

The exemplary apparatus, devices and systems can include a fully opencenter lumen, which can facilitate the insertion device/apparatus to beused to deliver any material, substance and/or agent, as well as for,collection, or introduction of other devices (e.g., medical devices)through the lumen. Thus, the exemplary apparatus, devices and systemscan be comparable to standard hypodermic needles, endoscopes,laparoscopes, cannulas, etc. which are generally characterized by theirinternal diameter. Further, the exemplary insertion device/apparatus canbe fully integrated and tuned to sense specific tissues and/or determinelocations of the tissue. The exemplary angle of the tip and/or the widthof the insertion apparatus/device described for the exemplaryembodiments can be provided and/or fabricated based on various differentcharacteristics of the tissue into which the exemplary insertiondevice/apparatus is inserted.

The exemplary optically-transmissive coating can be applied using aspray, sputtering, dipping, painting and/or deposition processes, asdiscussed below. Exemplary materials used for such application caninclude polymers such as, e.g., urethane, acrylic, polycarbonate,polystyrene, cyclic olefin polymers or copolymers, as well as copolymerscombining materials. It is also possible to utilize silicones. Glassand/or ceramic coatings can be formed using a sol gel process withpost-processing such as, e.g., sintering and/or by applying a materialin powder form and then using a melt quenching process. Other exemplarymaterials can include, e.g., silica glass, aluminum oxide, etc. Theselection of the exemplary materials that can be used for theapplication can be selected and/or defined by the process temperatureand compatibility with the target structure. For example, a glass or aceramic that prefers the use of the sintering procedure for theapplication of the coating may be difficult to apply to a polymerbecause the temperatures may be above the polymer glass transitiontemperatures. Thus, another exemplary material can be selected,according to the exemplary embodiment of the present disclosure.

According to further exemplary embodiments of the present disclosure,the resulting structure can then be used to produce the exemplaryinsertion device using conventional grinding and insertiondevice/apparatus fabrication processes. Additionally, the innerstructure (e.g., a base structure) can include the base body of theinsertion device/apparatus itself. The base structure can be made usingsimilar coating application as discussed herein.

Such exemplary base structure can be separated from theoptically-transmissive coating (e.g., which can be referred to as anoptically-transmissive core) via an optical cladding. Cladding materialscan include any material with a lower refractive index than thetransmissive coating of the base structure and/or that of the core. Suchexemplary materials include any of those described herein which have aslightly lower index than the coating of the base structure and/or thecore. The cladding may also include reflective materials such as, e.g.,a metallic coating.

According to still another exemplary embodiment of the presentdisclosure, selected areas on or in the insertion device/apparatus maybe masked or otherwise separated during the application of the claddingto leave selected areas uncoated. The mask may be applied in apredetermined pattern or shape. The mask may be applied manually, e.g.,by painting or printing on a substance that may be physically (peeling,scraping) or chemically removed after coating. The mask can also beapplied and patterned using a photolithographic process.

According to a further exemplary embodiment of the present disclosure,two, three, or more combinations of optically-transmissive core/claddingcan then be provided by applying additional layers to the insertiondevice/apparatus. Such exemplary multi-layer structure can be producedas discussed above, as well as using, e.g., a co-extrusion process. Forexample, one or more of the core/cladding combination(s) can be used todeliver optical radiation (e.g., light, etc.), and other one or more hecore/cladding combination(s) can be used to collect optical radiation(e.g., light, etc.).

FIG. 1A shows an exemplary diagram of an exploded cross-sectional sideview of a distal end of an exemplary insertion device/apparatus (e.g.needle) according to an exemplary embodiment of the present disclosure.As shown in FIG. 1A, the exemplary insertion device/apparatus caninclude a needle 105 incorporating two or more, non-planar, concentricconductive electrodes (e.g., electrodes 110 and 120). One of theelectrodes (e.g., electrode 110), can be formed from a conductivecoating on or in a surface of the insertion device/apparatus. The use oftwo or more, non-planar, concentric conductive electrodes can leavecenter lumen 125 open for delivery, collection, or introduction offluids or other substances or devices. The exemplary insertiondevice/apparatus can be of any size as required to inject apharmaceutical agent, or to introduce a minimally invasive device suchas a guidewire or catheter through opening 130. The exemplary electrodescan have different forms and/or configurations. For example, a portionof the insertion device/apparatus itself (e.g., a portion of the surfaceof the insertion device/apparatus) can act as one of the electrodes. Asecond electrode can then be fabricated in-situ and/or pre-fabricated,and then placed on the surface of the insertion device/apparatus. Thetwo electrodes can then be used to measure impedance at the tip of theinsertion device/apparatus (e.g., for the determination of the tissuetype as discussed herein).

As shown in FIG. 1A, center lumen 125 can be surrounded by electrode120, which can form an internal portion and/or surface of the insertiondevice/apparatus itself. An insulative coating 115 (e.g., made ofpolyimide or any other suitable material, such as polyamide, forexample) can surround electrode 120, e.g., outwardly radially. Electrode110 can then be formed around on insulative coating 115. Thus,insulative coating 115 can be used to electrically isolate electrodes110, 120 from one another. A second insulative coating, e.g., cansurround electrode 110, to isolate electrode 110, except for, e.g., anuninsulated portion 135 of electrode 110.

According to another exemplary embodiment of the present disclosure,another exemplary insertion device/apparatus can be provided, as shownin FIG. 1B. Indeed, the same exemplary portions/components of theexemplary insertion device/apparatus illustrated in FIG. 1A are labeledwith the same numerals in FIG. 1B. Similarly to the exemplary embodimentdescribed herein that provides the three-dimensional location of the tipof the exemplary insertion device shown in FIG. 1A, the exemplaryapparatus of FIG. 1B also can use alternating current applied to theexemplary electrodes to determine and/or infer a three-dimensionalposition of the tip of the exemplary apparatus. Nonetheless, instead ofproviding electrode 110 which circumferentially surrounds insulatinglayer 115, masking can be used to produce and/or providehelical-patterned and/or other exemplary patterned structures whichdefine an outer conductive patterned layer 110′. Such exemplary use ofthe helical-patterned outer conductive layer can improve thetransmission of the radiation and/or detection thereof by antennas 140,145, 150 to facilitate an improved three-dimensional position detectionof the tip of the exemplary insertion device. For example, referringagain to FIG. 1B, alternating current can be transmitted via theconductive/electrical channels of the device (e.g., internal theretoand/or provided on a surface thereof) to reach helically-patterned outerconductive layer (e.g., electrode) 110′ and/or inner conductive base(e.g., inner electrode) 120 so as to generate an electromagnetic field.Such electric field generated by patterned layer (e.g., concentricelectrodes) 110′ can be detected by antennas 140, 145, 150.

The exemplary insertion device/apparatus shown in FIG. 1B is illustratedin operation in FIG. 1C. In particular, exemplary concentric electrodes110′ illustrated in FIG. 1C facilitate locating the tip of the exemplaryinsertion device in a three-dimensional space, as discussed herein. Thiscan be done by using, e.g., static current, alternating current and/oranother energy or radiation which can include the determination ofimpedance at the tip. It is also possible to utilize a constant currentwith the exemplary electrodes 110, 110′, and 120. For example, constantor alternating current can be applied and/or utilized. For example, therelative distance of the tip to antenna's 140, 145, and 150 can bemeasured due to the current emission. In addition or alternatively, itis possible to provide other surface electrodes 140′, 145′, 150′ placedat different locations on the body to measure current and infer theeffective resistance and relative position from the tip to eachelectrode, e.g., in a three-dimensional space. In addition and/oralternatively, these exemplary electrodes 140′, 145′, 150′ placed atdifferent locations on the body can be used to measure the magnitude ofthe current which can decrease as a function of distance andresistance/impedance. Thus, using such electrodes 140′, 145′, 150′, itis possible to triangulate the position of the tip in thethree-dimensional space.

Turning to another exemplary embodiment of the present disclosure, FIG.1D shows an exemplary diagram of an exploded cross-sectional side viewof a distal end of an exemplary insertion device/apparatus (e.g. needle,endoscope, laparoscope, cannula, etc.) 110 a according to an exemplaryembodiment of the present disclosure. As shown in FIG. 1D, the exemplaryinsertion device/apparatus 110 a can include an optically-transmissivecoating 120 a which surrounds at least one portion of the insertiondevice/apparatus 110 a, e.g., in a location closer to a tip thereof. Forexample, such coating 120 a can be provided/formed/deposited on anexternal portion of the insertion device/apparatus 110 a, which forms awaveguide for the optical radiation. Thus, the coating 120 a can also bereferred to as an optical core and/or the waveguide which is configuredto transmit and/or receive optical radiation, e.g., light, etc. to andfrom tissue. A surface 150 a of a base structure 150 a of the insertiondevice/apparatus 110 a on which the coating 120 a isprovided/formed/deposited has a lower refractive index than theoptically-transmissive coating 120 a, such that the optical radiation isdirected along the coating 120 a toward the tissue of interest.

The insertion device/apparatus 110 a also includes a center lumen 130 aopen for delivery, collection, or introduction of fluids or othersubstances or devices. The center lumen is enclosed and/or defined by aninner surface of the base structure of the insertion device/apparatus110 a. Thus, as shown in FIG. 1D, center lumen 130 a can be surroundedby the base structure 160 a, which can form an internal portion and/orsurface of the insertion device/apparatus 110 a itself.

In one exemplary embodiment, the exemplary insertion device/apparatus110 a can be of any size as required to inject a pharmaceutical agent,or to introduce a minimally invasive device such as a guidewire orcatheter through the lumen 130 a.

FIG. 1E shows a further perspective view of an exemplary diagram of adistal end of the exemplary insertion device/apparatus 110 a accordingto an exemplary embodiment of the present disclosure of FIG. 1D. Asshown in FIGS. 1D and 1E, the exemplary insertion device/apparatus 110 awith the base structure 160 a is provided internally and surrounded bythe optically-transmissive coating 120 a, which can be provided using,e.g., sequential spray processes (e.g., as described herein) toprovide—internally to exemplary insertion device/apparatus 110 a, thecladding enclosed by the core.

In still another exemplary embodiment of the present disclosure, theexemplary apparatus can use the optical radiation (e.g., light) providedand/or returned from the sample to determine and/or infer athree-dimensional position of the tip of the exemplary apparatus withrespect to the tissue. For example, referring again to FIGS. 1A-1E,optical radiation can be transmitted via the core of the insertiondevice (e.g., provided along a surface thereof) to impact the tissuewith such optical radiation. The optical radiation can impact thetissue, and a responsive optical radiation can be provided from thetissue which can then be transmitted along the same coating 120/120 a(e.g., the core) as the insertion device/apparatus 110/110 a is beingtranslated, thereby providing signals which then converted to data toprovide, e.g., data and/or a visualization of the tissue surrounding theinsertion device/apparatus 110/110 a at a tip of thereof while it isbeing moved laterally through the body (e.g., through an orifice, via atubular structure of the body, such as gastro-intestinal tract, colon,etc.) For example, the insertion device/apparatus 110/110 a, e.g., viacoating 120/120 a (e.g., core) and/or the base structure (e.g., thecladding) can be connected to a computer, which can use such opticalreturn signals to determine information and/or visual data regarding thetissue surrounding the insertion device/apparatus. For example, thecomputer can be used to receive data from a spectrometer which collectsthe return optical radiation, and then can decipher the informationbased on the properties of the optical return radiation, and determinethe location of the tissue in question, its characteristics, the effectof the radiation impacting the tissue forwarded to the tissue, theeffect of other materials or agents supplied to the tissue and effectedby the radiation, etc.

Thus, for example, according to an exemplary embodiment of the presentdisclosure, the exemplary computer can generate and/or obtain images ofand/or regarding the tissue provided at or near the tip of the exemplaryinsertion device/apparatus 110/110 a using various imaging procedures,including but not limited to, e.g., magnetic resonance imaging (MM), CT,OCT, OFDI, etc. In addition, these exemplary procedures can be used toprovide detailed spatial information regarding the anatomical structureswhich are provided at or near the tip, as well as imaging one or moreportions of the anatomical structure using the three-dimensional specialinformation obtained using the above-described device.

It is also possible to utilize the insertion device/apparatus 110/110 ato provide optical radiation to the tissue of interest an effectiveamount of optical radiation to effect, disrupt, damage and/or treat thetissue. Such procedure can be useful as a photodynamic therapy fortreating, e.g., cancer and other deceases. For example, in one exemplaryembodiment of the present disclosure, upon providing the insertingdevice/apparatus 110/110 a into the body and reaching a particularlocation therein, a photosensitizing agent can be provided throughcenter lumen 130/130 a of the insertion device/apparatus 110 to adesired portion of the tissue. The coating 120 (e.g., the core) toprovide can be used as a waveguide to deliver optical radiation directlyto the area of the tissue where the photosensitizing agent was deliveredwith appropriate wavelength, power, etc. so as to effect, disrupt,damage and/or treat the tissue.

For example, the zone of influence from the coating 120/120 a (e.g., thecore) can be limited to the local area around the tip of the insertiondevice/apparatus. Such exemplary configuration can provide a high degreeof precision with limited localized damage. An exemplary application caninclude an application of the optical radiation of or to small, earlystage breast tumors, e.g., sized T1 or smaller. Other soft tissue tumorscan be treated as well, including regions in which RF ablation has beenpreviously performed including, e.g., the adrenal gland, bone, kidney,liver, lung, pancreas, thyroid, or prostate. The exemplary insertiondevice/apparatus can provide significant advantages in ablating varioustissues, including tumors and/or other lesions in highly sensitive areaswhere damage should be limited, including but not limited to the brain.In another example, arrays of exemplary assertion devices/apparatuswhich the exemplary components and/or configurations described hereincan be used to treat (e.g., ablate) larger areas, for example for skintightening. The exemplary configuration of exemplary insertiondevice/apparatus can be provided such that the exemplary area of thermaldamage around each exemplary insertion device/apparatus can be limitedthereby possibly reducing pain to the patient and/or decreasing recoverytime.

In addition, it is possible to utilize the information previouslyobtained regarding the determination of tissue type described hereinabove using the coating 120/120 a (e.g., core, waveguide, etc.) can bebased on the tissue determination via prior determination describedherein. For example, when the determination that the exemplary insertiondevice/apparatus has reached a particular tissue type provided via theinformation provided via the return optical radiation returning from thetissue via the coating 120/120 a (e.g., core, waveguide, etc.), theoperator and/or the computer can cause an optical source to transmitfurther optical therapy radiation to be transmitted to the coating120/120 a (e.g., core, waveguide, etc.), and effect, disrupt, damageand/or treat the tissue at the tip of the insertion device/apparatus110/110 a. The coating 120/120 a (e.g., core, waveguide, etc.) may alsobe used to further detect changes in the tissue due to treatment, e.g.,whether sufficient energy has been applied to effect, etc. the tissue.

For example, using the exemplary embodiments shown in FIGS. 1D and 1Ewhich utilize the coating 120 a as a single waveguide, can utilize amultiplexer to send and receive optical radiation. In this exemplarymanner, it is possible to decipher the information provided via theoptical radiation provided from or reflected from the tissue from theoptical radiation being forwarded to the tissue.

FIG. 1F shows a further perspective view of an exemplary diagram of adistal end of the exemplary insertion device/apparatus according toanother exemplary embodiment of the present disclosure. As shown in FIG.1F, the insertion device/apparatus can include a needle that can act asone of the electrodes 120 b, while multiple internal (to needle)coatings are used to produce a second electrode using sequential sprayprocesses (e.g., as described below) to provide—internally to needle—aninsulating layer, a second conductive layer, and a selective insulatinglayer 135 b which exposes a discrete part of the outer conductive layer.The electrical current can follow the shortest possible path from oneelectrode to the other, (e.g., at the very tip). There can also be somecontribution from the capacitive coupling through the insulatingcoating.

For the function of detecting/determining tissue types, based on thefrequencies of interest (e.g., the frequency used to detect the tissuetype), the outer insulating coating can be optional, although it can beused to provide protection for the outer conductive coating and/orlubrication to ease the insertion of needle which includes theelectrodes 120 b.

The exemplary insertion device/apparatus can include more than twolayers (e.g., more than two insulating and conducting layers). Forexample, additional layers can be applied to produce additionalelectrodes. In certain exemplary applications, it can be beneficial toutilize more than two electrodes to sense, detect and/or identify fluidsor tissues, for example, when the impedance of the fluid/tissue can belower than the impedance of the sensing electrodes themselves. (Seee.g., Reference 5).

According to another exemplary embodiment of the present disclosure, theexemplary insertion device/apparatus can be used to apply aradiofrequency (RF) signal to the tissue being inspected, thereby cause,e.g., ablation to a target area of the tissue. For example, referringagain to FIGS. 1F and 1G, energy can be transmitted via the conductivechannels of the device (e.g., internal thereto and/or provided on asurface thereof) to reach at least one of electrodes 110 b and 120 b.Due to such energy transmission, RF signals are applied across both ofthe electrodes 110 b, 120 b due to an insulating layer 135 b beingprovided there between. In this exemplary manner, the RF signaleffectuated by the energy provided by, e.g., one or more RF ablationgenerators would cause heating of specific tissues that are at or nearthe tip of the insertion device and/or at or near electrodes 110 b, 120b. For example, such RF source(s) can provide alternating RF field whichgenerates local RF heating. Thus, e.g., electrodes 110 b, 120 b canfacilitate the exemplary insertion device/apparatus to act as aprecision bi-polar RF ablation device/apparatus.

According to an exemplary embodiment of the present disclosure, the RFenergy generated by the RF ablation generator(s) may provide frequencyabove, e.g., about 200 kHz to reduce or minimize muscle stimulation.Other frequencies can be used, and are within the scope of the presentdisclosure. Conventional RF ablation generators generally operate atfrequencies between about 300 and 500 kHz. The waveform of the RF signalmay be modified by computer controlling the RF ablation generator(s) toadjust the effect on the tissue. For example, impendence can changeduring and after ablation.

In still another exemplary embodiment of the present disclosure, theexemplary apparatus can use alternating current applied to the exemplaryelectrodes to determine and/or infer a three-dimensional position of thetip of the exemplary apparatus. For example, referring again to FIGS. 1Fand 1G (as well as FIGS. 1A and 1C), alternating current can betransmitted via the conductive/electrical channels of the device (e.g.,internal thereto and/or provided on a surface thereof) to reach at leastone of the electrodes 110 b, 120 b so as to generate an electromagneticfield. Due to such alternating current transmission to one or both ofthe electrodes 110 b, 120 b, an electro-magnetic (EM) field can begenerated at the tip of the exemplary insertion device/apparatus. SuchEM field can be detected by one or more electromagnetic probes (e.g.,antennas) 140′, 145′, 150′ placed on or near the surface of the body.Such exemplary probes can facilitate, e.g., a triangulation of theposition of the tip of the exemplary insertion device/apparatus based onexemplary time of arrival of the signals at probes 140′, 145′, 150′and/or a strength of the received signal(s). For example, the probes140′, 145′, 150′ can be connected to a computer, which can use suchsignals to determine the location of the tip of the exemplary insertiondevice/apparatus in three-dimensional space.

According to the exemplary embodiment of the present disclosure, theexemplary computer can generate and/or obtain a three-dimensional imageof the tip of the exemplary insertion device/apparatus using variousimaging procedures, including but not limited to, e.g., magneticresonance imaging (MRI), CT, etc. In addition, these exemplaryprocedures can be used to provide detailed spatial information regardingthe anatomical structures which are provided at or near the tip, as wellas imaging one or more portions of the anatomical structure using thethree-dimensional special information obtained using the above-describeddevice.

This information may be used to improve positional accuracy by allowingthe positioning system to account for variations in EM propagation dueto different tissue types [Dove 2014]. Registration of the image withthe known 3D position will provide a means for detecting where the tipof the device is within the body. The EM field can operate within, e.g.,the Medical Implant Communication Service (MICS) frequency band (e.g.,about 402 to 405 MHz).

Such information can also be used for ablating the tissue and/ordetermining the type of the tissue under examination. For example, thealternating current can produce an electromagnetic (EM) field at the tipof the exemplary apparatus which can be detected using, e.g., one ormore electromagnetic probes (antennas) placed on or near the surface ofthe body. The exemplary probe(s) can facilitate, e.g., a triangulationof the position of the tip of the exemplary apparatus from time ofarrival and/or signal strength data.

The exemplary embodiment described herein can provide thethree-dimensional location of the tip of the exemplary insertion deviceshown in FIG. 1A, the exemplary apparatus of FIGS. 1F and 1G also canuse alternating current applied to the exemplary electrodes to determineand/or infer a three-dimensional position of the tip of the exemplaryapparatus. Instead of providing electrode 110 a which circumferentiallysurrounds insulating layer 135 b, masking can be used to produce and/orprovide helical-patterned and/or other exemplary patterned structureswhich define an outer conductive patterned layer 110 b. Such exemplaryuse of the helical-patterned outer conductive layer can improve thetransmission of the radiation and/or detection thereof by antennas 140′,145′, 150′ to facilitate an improved three-dimensional positiondetection of the tip of the exemplary insertion device. For example,referring again to FIGS. 1F and 1G, alternating current can betransmitted via the conductive/electrical channels of the device (e.g.,internal thereto and/or provided on a surface thereof) to reachhelically-patterned outer conductive layer (e.g., electrode) 110 band/or inner conductive base (e.g., inner electrode) 120 b so as togenerate an electromagnetic field. Such electric field generated bypatterned layer (e.g., concentric electrodes) 110 b can be detected byantennas 140′, 145′, 150′.

For example, in operation, exemplary concentric electrodes 110 billustrated in FIGS. 1F and 1G can facilitate locating the tip of theexemplary insertion device in a three-dimensional space, as discussedherein. This can be done by using, e.g., static current, alternatingcurrent and/or another energy or radiation which can include thedetermination of impedance at the tip. It is also possible to utilize aconstant current with the exemplary electrodes 110 a, 120 b. Forexample, constant or alternating current can be applied to the treatmentdevice. For example, the relative distance of the tip to antenna's 140,145, 150 (e.g., as shown in FIGS. 1A and 1C) can be measured due to thecurrent emission. In addition or alternatively, it is possible toprovide other surface electrodes 140′, 145′, 150′ placed at differentlocations on the body to measure current and infer the effectiveresistance and relative position from the tip to each electrode, e.g.,in a three-dimensional space. In addition and/or alternatively, theseexemplary electrodes 140′, 145′, 150′ placed at different locations onthe body can be used to measure the magnitude of the current which candecrease as a function of distance and resistance/impedance. Thus, usingsuch electrodes 140′, 145′, 150′, it is possible to triangulate theposition of the tip in the three-dimensional space.

Turning to a still another exemplary embodiment of the presentdisclosure, the exemplary insertion device/apparatus can be providedwhich can be used to be include a structure and/or configuration thatcan sense and/or generate vibration over a wide range of frequencies.For example, as shown in FIG. 1F, an internal structure (e.g., as theinner electrode) 120 b can be provided, which enclosed and/or encircledby an inner piezoelectric coating 160 b, which in turn is encompassedand/or encircled by a conductive coatings (e.g., an outside electrode)110 b externally on the exemplary insertion device/apparatus. Forexample, current—such as an alternative current—can be directed toconductive coating 110 b and/or internal structure 120 b which areseparated from one another by inner piezoelectric coating 160 b. In oneexemplary embodiment, such energy transmission through this exemplaryconfiguration can facilitate a mechanical vibration of the exemplaryinsertion device/apparatus. Thus, if the insertion device/apparatus isconnected to a laparoscopic/endoscopic instrument 170 b that has acutting/clamping arrangement 180 b provided thereon or therein (e.g.,jaws, etc.), as shown in FIG. 1G, such mechanical vibration would beable to cause an actuation of the such exemplary laparoscopic/endoscopicinstrument 170 b, which in turn can actuate the cutting/clampingarrangement 180 b (e.g., by vibrating one or both of the jaws) to modifythe tissue, e.g., by cutting into tissue of interest which is providedat or near such cutting arrangement 180. The same cutting/clampingarrangement 180 b can be used to clamp the tissue of interest when thevibration by electrodes 110 b, 120 b is effectuated. In anotherexemplary embodiment according to the present disclosure, the exemplaryconfiguration of electrodes 110 b, 120 b and inner piezoelectric coating160 b can be used to detect the mechanical vibration of the exemplaryinsertion device/apparatus. For example, antennas can be placed in thevicinity of the exemplary insertion device/apparatus to detectultrasound vibrations which are produced using the exemplaryconfiguration when the exemplary insertion device/apparatus or partthereof (e.g., the tip) is vibrating. Such information is passed to thecomputer processor, which provides information to cutting/clampingarrangement 180′ of exemplary laparoscopic/endoscopic instrument 170 bof FIG. 1G to perform, e.g., cutting, clamping and/or other relatedfunctions.

FIG. 2A shows a further perspective view of an exemplary diagram of adistal end of the exemplary insertion device/apparatus according to anexemplary embodiment of the present disclosure. As shown in FIG. 2, theinsertion device/apparatus can include a needle 120 of FIGS. 1A-1C thatcan act as one of the electrodes 120, while multiple internal (toneedle) coatings are used to produce a second electrode using sequentialspray processes (e.g., as described below) to provide—internally toneedle—an insulating layer, a second conductive layer, and a selectiveinsulating layer 135 which exposes a discrete part of the outerconductive layer. The electrical current can follow the shortestpossible path from one electrode to the other, (e.g., at the very tip).There can also be some contribution from the capacitive coupling throughthe insulating coating.

For the function of detecting/determining tissue or fluid types, basedon the frequencies of interest (e.g., the frequency used to detect thetissue or fluid type), the outer insulating coating can be optional,although it can be used to provide protection for the outer conductivecoating and/or lubrication to ease the insertion of needle 120.

FIG. 2B shows another exemplary embodiment of the present disclosure foran exemplary insertion device/apparatus 110′, and shall be describedherein with reference to the components shared with the exemplaryembodiments illustrated in FIGS. 1D and 1E and described herein includesall of similar components as referenced herein therefor. For example, asshown in FIG. 2B, the insertion device/apparatus 110 a includes thecoating 120 a (e.g., the core, waveguide, etc.), which is applied orprovided over a cladding 170 a, which itself is applied or provided overthe base structure 160 a. For example, optical radiation can be providedover the coating 120 a (e.g., the core), and directed to the tissue. Dueto the cladding 170 a having a different optical characteristics, thecoating 120 a acts more effectively as a waveguide for the opticalradiation, as the cladding 170 a prevents scattering of the opticalradiation provided via the cladding 120 a, thereby directing the opticalradiation as would a waveguide. Further, due to the possibility of thecladding 170 a being also optically-transmissive, although withdifferent characteristics from those of the coating 120 a, it ispossible to utilize the coating 120 a (e.g., core, waveguide) totransmit the optical radiation in one direction, while transmittingseparate optical radiation in another direction. In this exemplarymanner, it is possible to transmit the optical radiation to the tissuevia the coating 120 a, and then provide the optical radiation from thetissue via the cladding 170 a (or the reverse).

According to further exemplary embodiments of the present disclosure, anexemplary insertion device/apparatus 110″ of FIG. 2C can be providedwhich can include more than two layers (e.g., more than one combinationof the outer optically-transmissive coating (e.g., core) 120″ and thecladding 170 a. For example, in the same manner as described hereinabove for the exemplary embodiments of FIGS. 1D, 1E and 2B, additionallayers can be applied to produce the above-described core/claddingcombination. In such exemplary embodiment, the cores (e.g., coatings,waveguides) 120 a can be used to transmit optical radiation to thetissue, and the claddings 170 a can be used to receive the opticalradiation from the tissue. Further, it is possible to use one or more ofthe core/cladding combinations for transmitting the optical radiation tothe tissue, while another one or more of the core/cladding combinationsfor receiving the optical radiation from the tissue. Thus, thetransmission of the radiation using multiple cores and claddings (e.g.,performed in parallel or in series) and the deciphering thereof by thecomputer can expedite the transmission of the optical radiation and theprocessing/deciphering of the received optical radiation.

According to another exemplary embodiment of the present disclosure,another exemplary insertion device/apparatus 110″ can be provided, asshown in FIG. 2C. Indeed, the same exemplary portions/components of theexemplary insertion device/apparatus illustrated in FIGS. 1D and 1E arelabeled with the same numerals in FIG. 2C. Nonetheless, instead ofproviding a single coating which is applied on and circumferentiallysurrounds the base structure 160, masking can be used to produce and/orprovide helical-patterned and/or other exemplary patterned structures ofa coating which define outer waveguides 120″. Such exemplary use of thehelical-patterned outer waveguides 120″ (e.g., coatings) can improve thetransmission of the optical radiation to facilitate an expeditedtransmission of the radiation, e.g., which can be performed in parallel.For example, referring again to FIG. 2C, optical radiation can betransmitted along the waveguides 120″ of the device (e.g.,—provided onthe surface of the base structure 160, which can be separated by asplitter into individual ones of the waveguides 120″. The separatedoptical radiation portions emitted from such individual waveguides 120″are forwarded to the tissue structure at different locations thereofwhich correspond to the locations of the individual waveguides 120″situated on the base structure 160. The return optical radiation can besimultaneously or serially received by the same individual waveguides120″ which emitted the radiation being forwarded to the tissue, or byother adjacent or non-adjacent waveguides 120″.

FIG. 2D illustrates perspective views of the exemplary embodiment of thepresent disclosure which is very similar to the exemplary embodimentshow in FIG. 2C. As described herein, the same components illustrated inFIG. 2C shall be numbered in the same manner in FIG. 2C, except that thecladding 170 a is provided between the base structure 160 a and thecoating/core 120″. In particular, as provided in FIG. 2C, the waveguides120″ are shown as core coating sections 121 a, 122 a, which are separatefrom one another by a cladding coating section (of the cladding 160 a),which is the followed (following the coating section 121 a) by acladding coating section. In this exemplary configuration shown in FIG.2D, similar operation can be performed as described herein above, andthe insertion device 110′″ can be used in the same manner as describedherein with respect to the insertion devices according to otherexemplary embodiments, e.g., with reference to FIGS. 2B and 2C. Forexample, as provided in FIG. 2D, cladding coating sections (and thus thecladding 170 a), and the core coating sections 121 a, 122 a (and thusthe coating/core 120″) can be provided over the cladding 170 a. The corecoating sections 121 a, 122 a can be separated from one another by thecladding section 171 a, and another cladding section can 172 a followthe core coating section 122 a. In this exemplary manner, it is possibleto provide an emission of the optical radiation via different sectionsof the core 120″ and/or the cladding 170 a to and from the tissue, e.g.,in a similar manner as described herein above with respect to theexemplary embodiment shown in FIG. 2C. For example, according oneexemplary embodiment, the optical radiation forwarded to the tissue canbe provided via the cladding coating sections 171 a, 172 a (and thus viathe cladding 160 a), and the optical radiation returning from the tissuecan be provided via the core coating sections 121 a, 122 a (and thus viathe core 120″). Of course, the reverse optical radiation transmissioncan be effectuated as well, e.g., the optical radiation forwarded to thetissue can be provided via the core coating sections 121 a, 122 a (andthus via the core 120″), and the optical radiation returning from thetissue can be provided via the cladding sections 161 a, 162 a (and thusvia the cladding 160 a).

The exemplary insertion device/apparatus can include more than twolayers (e.g., more than two insulating and conducting layers). Forexample, additional layers can be applied to produce additionalelectrodes. In certain exemplary applications, it can be beneficial toutilize more than two electrodes to sense, detect and/or identify fluidsor tissues, for example, when the impedance of the fluid/tissue can belower than the impedance of the sensing electrodes themselves. (Seee.g., Reference 5).

FIG. 3 shows an exemplary diagram of a method 300 for applying layers tothe exemplary insertion device/apparatus according to an exemplaryembodiment of the present disclosure. As shown in FIG. 3, themulti-layer structure of the insertion device/apparatus can be producedby applying the layers with a spray process using, for example, aninsulating and a conductive and/or optically transmissive ink. Forexample, at procedure 305, a base hypotube can have an insulatingpolyimide coating applied thereto at procedures 310 and 315. Atprocedure 320, a silver conductive coating can be applied to the tube,and at procedure 325, the tube can be cut to length, and the tip of theinsertion device/apparatus can be created by, e.g., grinding or lasercutting. Element 330 illustrates a bottom view of the finished insertiondevice/apparatus (e.g., needle, cannula, endoscope, laparoscope, etc.),and element 335 shows a side view of the finished insertiondevice/apparatus.

The exemplary procedure shown in FIG. 3 can limit the coatings to theoutside of the tubing/needle leaving the center open. For example,eliminating masking and etching can keep the process for applying thelayers relatively simple. After each procedure, the structure can beheated to remove any solvent, and to polymerize the coating.

FIG. 4A shows an exemplary image of exemplary needle 405 according to anexemplary embodiment of the present disclosure. For example, exemplaryneedle 405 was produced from 26 Ga 316SS tubing using the exemplarymethod shown in FIG. 3. The conductive coating on needle 405 wasproduced using a conductive silver ink (e.g., Creative Materials118-43T). The base insulating coating is a polyimide (e.g., Jaro 650).As shown in FIG. 4A, needle tip 410 was laser cut. It should beunderstood that the tip of needle 450 can also be fabricated using othersuitable techniques used to produce exemplary needles according to theexemplary embodiment of the present disclosure, such as, for example,grinding.

FIG. 4B shows an exemplary close-up image illustrating the structure ofthe exemplary needle fabricated with a layer of polyimide (e.g.,insulating layer 505 surrounding a stainless steel body 510) and anouter layer 515 composed of a silver conductive ink. Both insulatinglayer 505 and outer layer 515 were applied using an exemplary sprayprocess (e.g., as described above in FIG. 3). According to an exemplaryembodiment of the present disclosure, the sharp tip of exemplary needle405 can be formed using a grinding process after the coatings (e.g.,insulating layer 505 and/or outer layer 515) are applied to stainlesssteel body 510. The tip can be formed using a grinding process after thecoatings were applied to the stainless steel body.

The exemplary geometry, called a tri-bevel tip, can be formed throughmultiple grinding processes. For example, first, a primary grind can beapplied at an angle, e.g., a, relative to the central axis of thecylindrical body. This grinding procedure can form a flat surface.Second, a secondary grind can be formed by rotating the cylindrical bodya fixed angle, e.g., β, around the central axis and then grinding thesecondary surface relative to the flat surface generated by the initialprocedure. This exemplary procedure can be repeated by rotating the bodyin the opposite direction, e.g., negative β. The resulting surface ofeach bevel can be, e.g., flat and continuous. For example, variousexemplary angles and ranges of angles for a can be 12°, 12-14°, 15-17°,18-22°, 23.5°, 23-25°, 26-31°, 30° and/or 45°, including 12-45°. Theeffective exemplary average of α and β when viewed from the side canprovide the following various exemplary angles and ranges of angles:12°, 13°, 15°, 19°, 20°, 22° and 23.5°, including all the angles withinthe range of 12-24°. In one example,

α effective exemplary average of α and β 12-14° 13° 23-25° 19° 21-22°20° 26-31° 22° 23.5°    23.5°.

FIG. 5 shows an exemplary image of exemplary needles 505 produced usinga grinding process according to an exemplary embodiment of the presentdisclosure. The layers of exemplary needles 505 can be produced throughprocedures other than spray coating such as electrochemical deposition,vapor deposition or sputtering, although not limited thereto. Maskingcan also be used to produce geometric patterns during the coatingprocess. Alternatively or in addition, a mask can be applied after thecoating, similar to the exemplary process used to produce printedcircuit boards. In such an example, the mask can be spared duringchemical etching.

FIG. 6 shows a set of side cross-sectional view and exemplary diagramsof needles 600 having different conductive traces according to anexemplary embodiment of the present disclosure. For example, asillustrated in FIG. 6, needle 600 can include an insulating coating 605,which can be used to insulate a single conductive trace 615 located onthe surface of needle 600. Another needle 650 can also include aninsulating coating 605. Further, needle 650 can include multipleconductive traces (e.g., traces 620, 625) on the surface of needle 650.

In conjunction with the exemplary embodiment shown in FIG. 6, theelectrodes can be fabricated on the surface of a needle using proceduressuch as pad printing or screen printing with an outer insulating layerapplied after. The insulating coating can be printed, deposited, orapplied in the form of shrink tubing.

FIG. 7 shows an exemplary image of an exemplary needle 705 having asurface electrode that was pad printed using ink according to anexemplary embodiment of the present disclosure. Exemplary needle 705 isa conventional 26 Ga hypodermic needle. The conductive surface electrodewas pad printed using an ink specifically formulated for pad printing(e.g., Creative Materials 118-43T).

FIG. 8 shows an exemplary close-up diagram of the distal end of theexemplary insertion device/apparatus (e.g., needle) having electrodes805, 810 patterned on the insertion device/apparatus according to anexemplary embodiment of the present disclosure. The spacing betweenelectrodes 805, 810 can be varied to produce a physical filter to tailorsensitivity to different size structures. For example, the electrodescan be separated such that the spacing can be greater than the size of aspecific artery. In such exemplary case, the electrodes should not beboth be inside a blood vessel (e.g., an artery, a vein, etc.) at thesame time which can affect electrical impedance.

FIG. 9A shows an exemplary image of an exemplary insertion apparatus 900with an exemplary needle 905 according to another exemplary embodimentof the present disclosure. Electrodes connected to needle 905 can alsobe electrically connected to an external instrument using wires, cables,or a flex circuit terminated with a connector. The flex circuit can forma flex cable for connection to the instrument. A connector 910 with twoor more electrical contacts can be used to provide an electricalconnection to the needle 905, contacting the needle body (e.g.,electrode 1) as well as the outer conductive coating (e.g., electrode 2)and/or any additional external electrodes formed with alternatingconcentric insulating and conducting layers. As shown in FIG. 9A, theelectrodes (e.g., which can be electrodes 110 b, 120 b of FIGS. 1F and1G and or conductive coatings thereof) can be connected to the externalinstruments via connectors 920, 930, and electrodes/conductive coatingsat such locations are uncovered by any isolating layer or coating (e.g.,exposed). This uncovered section may be formed by either masking thesection during the coating process or by mechanically or chemicallyremoving the coating.

FIG. 9B illustrates a perspective view of the exemplary insertiondevice/apparatus 940 according to another exemplary embodiment of thepresent disclosure, with FIG. 9C providing a side view of such exemplaryinsertion device/apparatus of FIG. 9B with the tip thereof extending ina downward direction. Similarly to the exemplary embodiment of theexemplary insertion device/apparatus shown in FIG. 9A, the exemplaryinsertion device/apparatus 940 of FIGS. 9B and 9C includes an exemplaryneedle 950. Electrodes connected to needle 950 can be electricallyconnected to an external instrument via an electrical connection section960 using, e.g., wires, cables, flex circuit terminated with a connector(similar to the flex circuit described herein), etc. FIG. 9D illustratesa cross-sectional exploded side view of an electrical connection sectionof the exemplary insertion device/apparatus shown in FIGS. 9B and 9C.

For example, as shown in FIGS. 9B-9D, a first electrical connector 971can be connected (e.g., soldered) to an outer electrode (or an outerelectrical conductive coating of needle 960), i.e., contacting theneedle body via such electrode 1 and/or outer conductive coating.Further, a second electrical connector 972 can be connected (e.g.,soldered) to an inner electrode (or an outer electrical conductivecoating of needle 960), i.e., contacting the needle body via suchelectrode 2 and/or inner conductive coating, Indeed, second electricalconnector 972 can be connected to the inner conductor/conductive coatingwithout being covered by any resistor or resistive coating, i.e., theelectrode/conductive coating can be exposed. First and/or secondelectrical connectors 971, 972 can also be connected to additionalexternal electrodes formed with alternating concentric insulating andconducting layers.

Similarly to the exemplary embodiments illustrated in FIG. 9A, theelectrodes of FIGS. 9B-9D (e.g., which can be electrodes 110 b, 120 b ofFIGS. 1F and 1G and or conductive coatings thereof) can be connected tothe external instruments via first and second electrical connectors 971,972, and electrodes/conductive coatings at such locations are uncoveredby any isolating layer or coating (e.g., exposed). Again, similarly tothe previously-described exemplary embodiment, such uncovered sectionmay be formed by either masking the section during the coating processor by mechanically or chemically removing the coating. Thereafter, e.g.,electrodes 971, 972 can be connected to external components using anelectrically conductive cable 980, as shown in FIG. 9E which illustratesa side-view image of the exemplary insertion device/apparatus of FIGS.9B-9D. Such exemplary embodiments of the exemplary insertiondevice/apparatus 900, 940 as illustrated in FIGS. 9A-9E can beproduced—according to one exemplary non-limiting embodiment of thepresent disclosure—starting with, e.g., a coated tubing, e.g., 316SStubing coated with 0.001″ polyimide and 0.001″ silver conductive ink canproduce a bi-polar electrode at the exposed tip.

FIG. 10A shows an exemplary image of an exemplary needle 1005 havingmagnetic wires attached thereto according to an exemplary embodiment ofthe present disclosure. FIG. 10B shows an exemplary diagram of theexemplary needle 1005 shown in FIG. 10A illustrating the attachment ofthe magnet wire according to an exemplary embodiment of the presentdisclosure. An exemplary needle was made using, for example, a 26 Ghypodermic needle 1005 and 34G magnet wire 1010 that is at least twicethe size (e.g., length) of the hypodermic needle. The needle 1005 actedas one electrode and the exposed end of the magnetic wire was the secondelectrode. Magnetic wire 1010 is threaded through hypodermic needle 1005and glued to the inner surface of the needle using cyanoacrylate. Needletip 1015 is flush with the end of magnetic wire 1010. The other end ofmagnetic wire 1010 is stripped of its insulation. The exemplaryinsertion (e.g., needle) apparatus shown in FIGS. 10A and 10B wasconnected to an inductance (L), capacitance (C), and resistance (R)(“LCR”) meter to measure impedance. One test lead connected to thehypodermic needle and the other test lead connected to the stripped endof the magnet wire.

FIG. 10C shows an exemplary graph illustrating impedance versusfrequency for various tissue types (e.g., dermis 1105, fat 1110, blood1115, kidney 1120, and heart 1125) according to an exemplary embodimentof the present disclosure. In order to measure the impedance versusfrequency, the needle was inserted into various tissues and fluids in alarge rabbit to determine variations in measured impedance withdifferent frequency signals. The rabbit was sacrificed before testing.Results shown in the graph in FIG. 11 demonstrate that the exemplaryapparatus provides clear, measureable, differences between tissue andblood. While various exemplary frequencies can be used, acceptableresults to resolve the difference between blood and various tissues canbe achieved at frequencies between 1000 Hz and 100,000 Hz based on aseparation in the measured impedance between the results obtained fromdifferent samples.

Additional in-vivo testing was performed using fully integratedelectrodes produced using the pad printing procedure as described above.Testing was performed in a live New Zealand White rabbit to measureimpedance in several different types of tissue. A cutdown was performedto expose major blood vessels in the rabbit's neck and thigh. Theexemplary needles were inserted into different tissues to differentdepths. Magnet wire was used to connect the electrodes to an impedanceanalyzer (e.g., Keysight 4294A/1D5). Measured impedance (e.g., magnitudeand angle) was exported to text files.

FIG. 11 shows a set of side cross-sectional views of another exemplaryembodiment of the exemplary insertion apparatus 1100 which provides anexemplary sensing technology implemented in the form of a cannula,according to yet another exemplary embodiment of the present disclosure.As illustrated in FIG. 11, a cannula body 1115, 1115′ of an injectioncannula 1100 can be coated (e.g., with an insulating coating 1120) toproduce a sensing structure around the cannula openings 1120, 1120′.FIG. 13 shows an exemplary diagram illustrating that information can bewirelessly transmitted from a transmitted of the exemplary insertion(e.g., needle) apparatus 1305 for use in determining the tissue typeaccording to an exemplary embodiment of the present disclosure. Forexample, an exemplary processor, microprocessor, etc. can be embedded ineither at any portion of the needle apparatus 1305, including but notlimited in the needle itself, which can be used to collect theelectrical information obtained using the electrodes. This informationcan be sent to another device (e.g., using a wired or wirelesstransmission medium, as discussed below), which can be used to analyzethe information, determine the impedance, and ascertain the tissue type.

FIG. 14 shows an exemplary diagram of an exemplary mobile device 1405used to receive the wireless transmission of information from theexemplary insertion (e.g., needle) apparatus illustrated in FIG. 13 todetermine the tissue type according to an exemplary embodiment of thepresent disclosure. For example, exemplary needle apparatus 1305 canhave a wireless communication chip embedded therein (including in anypart thereof, such as the needle, etc.), which can be powered using aninternal battery, through an external electrical connection, or throughany suitable wireless power medium. The power supplied to needleapparatus 1305 can be used to power the wireless communication chip, aswell as any microprocessor embedded in needle apparatus 1305.Alternatively, power can be obtained from electrical signals present inthe body of the subject, which can provide sufficient power to send aburst signal of information from needle apparatus 1305 to device 1405.

The exemplary tissue detection system/apparatus can include a singleinsertion device/apparatus (e.g., a needle, a cannula, etc.). However,the exemplary tissue detection system/apparatus can include a pluralityof insertion devices (e.g., an array of needles, an array of cannulas,an array of mixture of needle(s)/cannula(s), etc.). Each insertiondevice in the array thereof can be of the same electrodedesign/structure (e.g., one design of the various exemplary electrodedesigns/structures described above). However, each insertion device inthe array can have a different design/structure, or a subset of theinsertion devices can have one design/structure while another subset canhave a different design/structure. Each insertion device in theexemplary array thereof can perform tissue detection as described above,and each insertion device can also perform a medical function (e.g., theadministering of a material or a substance or the removal of a biopsysample and/or other fluid, tissue, cells or material). Thus, one or moreinsertion devices in the exemplary array thereof can perform the tissuedetection, while one or more other needles can perform themedically-related functions. The exemplary array of the insertiondevices can also be used to increase the accuracy of the tissuedetection by increasing the number of the electrodes that are used todetermine the impedance. Additionally, a comparison of the impedancebetween the insertion devices in the array can also be used to determinethe tissue type.

Exemplary Operation and Determination of Tissue Type

The exemplary insertion device/apparatus can be used to measureimpedance around the tip of the needle. Impedance, Z can be a measure ofthe opposition of a medium to alternating current flow at a givenfrequency. Z can be defined by, for example:

Z=R+jXc

where R can be resistance and Xc can be reactance. Resistance can varywith geometry and resistivity of the medium. Reactance can vary withfrequency and capacitance.

As the exemplary insertion device/apparatus passes through the differenttissues, the instrument can read the impedance and phase angle at theneedle tip at a fixed frequency, for example, 10,000 Hz. As theexemplary insertion device/apparatus passes through different types oftissue, the measured/inferred impedance can show a distinct change.Electronics integrated into the hub of the exemplary insertiondevice/apparatus can provide a measurement of the current. The exemplaryapparatus can be used to provide either a warning (e.g., to avoid aprocedure) or a helpful alert (e.g., to proceed with a procedure).

The exemplary insertion devices/apparatuses can be used as a replacementfor current disposable hypodermic needles. Potential uses can includeinjection and minimally invasive instrument introduction. During aninjection procedure, for example a filler injection, the clinician caninsert the exemplary insertion devices and manipulate the needle as pernormal operation. For example, as the exemplary insertiondevice/apparatus penetrates a blood vessel (e.g., an artery, a vein,etc.), the exemplary apparatus can provide an audible and/or a visualalert to warn the clinician that it may be hazardous to inject aparticular material (e.g., the filler). For other types of injections,for example, an intradermal vaccine injection, a clinician can beprovided with an indication that the needle is in the intradermal spacein which case, the clinician can wait for an alert before injecting.

Electrical connections can be made to connect the electrodes to theelectronics that can sense and interpret the electrical impedance. Theelectronics can be integrated into the needle, as close as possible tothe electrodes. Exemplary electronics can include a source to generatean oscillating voltage and a measurement device to determine themagnitude and phase between the applied voltage and the current. Theelectronics can be packaged to be integrated into the hub of theexemplary insertion device/apparatus which can typically be used toconnect the exemplary insertion device/apparatus to a syringe. Forexample, Analog Devices manufactures a single chip in an 8 mm×8 mmpackage, the ADuCM350, which can be used to analyze impedance over awide range of frequencies. Such exemplary chip can easily fit within theenvelope of a standard Luer hub. The connection between the electrodesand the integrated electronics can be made using traces produced at thesame time as the electrodes. The ADuCM350 chip can contain an audiodriver which can be used to produce an audible sound to alert a userwhen the exemplary insertion device/apparatus has been inserted intoand/or penetrated a specific tissue structure.

The exemplary electronics can communicate wirelessly with an externalreceiver for further processing. Wireless communication can be performedusing any low power hardware, for example Bluetooth LE, ANT, RF, orZigbee. The exemplary apparatus can be tailored to focus on the responseat a very narrow band of frequencies rather than across a broadspectrum. Therefore, custom electronics tailored for a specific tissuetype can be much simpler than a general analyzer. The exemplaryinsertion device/apparatus can be further simplified by offloadingprocessing to an external console. The electronics on the exemplaryinsertion device/apparatus can be limited to simply measuring thecurrent in response to the input, transmitting the response to theconsole via a low power RF or other transmission scheme.

Exemplary Biopsy Operation

FIG. 22A shows an exemplary diagram of an exemplary device for use incore biopsies, according to an exemplary embodiment of the presentdisclosure. FIG. 22B shows an exemplary diagram of the cross-section ofthe exemplary device shown in FIG. 22A, according to an exemplaryembodiment of the present disclosure. As shown in FIGS. 22A and 22B, theexemplary core biopsy needle 2200 can incorporate a central needle 2205with a sharpened point 2210 and a concave section 2215 proximal from thepoint. Concave section 2215, which can be referred to as a bowl, can bethe region in which a tissue sample is collected and retained. Once theneedle point 2210 is positioned in the desired location in the tissue,an outer sleeve 2220 with a sharpened edge advances to cut/shear tissue,capturing the desired sample between sleeve 2220 and needle 2200. Corebiopsy needles can be placed using ultrasound imaging, magneticresonance (MR) imaging, or stereotaxis imaging. Approximately 2.8% ofcore biopsies result in false negative diagnoses.

As shown in FIG. 22A, concentric coatings 2225 and 2230 can be appliedto the needle material prior to be ground and formed into the finalshape. The grinding of the point and the bowl section can expose theedges of the coatings. This can produce a dual electrode structure atthe point, and also in the region of the bowl as illustrated in FIGS.22B and 22C. FIG. 22C shows an exemplary diagram of needle 2200 beinginserted into a mass 2235 in a breast, according to an exemplaryembodiment of the present disclosure.

This structure of the core biopsy needle can facilitate sensing duringinitial needle guidance and also during collection. The sensingstructure of the needle point can facilitate impedance measurement asthe needle is advanced through tissue to the target location, which cantypically be abnormal tissue identified through imaging. The structurecan also facilitate sensing of tissue impedance within the bowl. Sensingthe impedance of tissue located in the region of the bowl can facilitatethe confirmation that the tissue is abnormal prior to collection. Acombination of sensing during advancement, and just prior to collection,can aid in the reduction of false negatives due to incorrect placementof a core biopsy needle.

FIG. 22D shows an exemplary image of the exemplary device shown in FIG.22A inserted into a mouse and a set of exemplary graphs illustrating theresulting measurements, according to an exemplary embodiment of thepresent disclosure. Some abnormal, cancerous tissue can be highlyvascularized. This can produce a structure with distinct differences inelectrical impedance that can be determined from surrounding,non-cancerous tissue. Vascularized tumors can occur anywhere in thebody. Exemplary measured impedance data that can be representative oftarget abnormal tissue is shown in FIG. 22D, which illustrates datacollected in mice afflicted with melanoma. The data illustrates 1)measured impedance magnitude as the coated, 26 Ga sensing needle,advances through the cancerous tissue and into normal tissue, and 2) acomparison of static measured impedance magnitude from cancerous tissueand normal muscle. The cancerous tissue shows measured impedancemagnitude in the range of 1,000 Ohms to 2,000 Ohms while normal muscleshows measured impedance between 2,000 Ohms and 5,000 Ohms.

Exemplary Additional Discussion

As discussed herein, the exemplary insertion device/apparatus can beused in various injection procedures which require injection intospecific tissues such as fat, septae, or the intradermal space. Theexemplary insertion device/apparatus can also be used in cardiaccatheterization (e.g., trocars), which can be used to introducecatheters into a blood vessel (e.g., an artery, a vein, etc.). Theexemplary insertion device/apparatus can be used in various otherapplications including, but not limited to, anesthesia procedures, aswell as during ablation procedures to determine when the ablationelectrodes are within a specific tissue type. The exemplary insertiondevice/apparatus can be integrated into a catheter to be used inside thebody. For example, the insertion device/apparatus can be used as part ofa transceptal needle, which can be used during minimally invasivecardiac procedures. Any suitable fabrication procedure/technique can beused to produce printed circuit boards can be used to produce theexemplary insertion device/apparatus structure. Exemplary electrodes canbe rigid or flexible.

FIGS. 19A-19C are exemplary flow diagrams of exemplary methods 1900,1940, and 1970 for determining a type of a tissue of a subject using theexemplary insertion device/apparatus. For example, as shown in FIG. 19A,at procedure 1905, a first electrically conductive layer in theinsertion device/apparatus can be electrically isolated from a secondelectrically conductive layer in the insertion device/apparatus using aninsulating layer. At procedure 1910, the insertion device/apparatus canbe inserted into the portion of the subject to reach the tissue. Atprocedure 1915, a first electrical signal can be transmitted and/orreceived using the first electrical conductive layer, whichcircumferentially surrounds a lumen of the insertion device/apparatus.In one exemplary embodiment of the present disclosure, the AC wave formthat was generated can pass through analog conditioner circuitry to theelectrode(s). Impedance measurement of tissue between electrodes canimpact the wave form which can then be measured using exemplary digitalprocessing techniques (e.g., synchronous detection, 4fs, etc.) Atprocedure 1920, the electrical signal (or another electrical signal) canbe received from the second electrically conductive layer, whichcircumferentially surrounds the first electrically conductive layer. Atprocedure 1925, an impedance can be determined based on the ratio of thetransmitted and received electrical signals. At procedure 1930, thetissue type can be determined based on the impedance. In one exemplaryembodiment, feedback may be given to the user by providing appropriateinformation to the user to an optical display, auditory device or ahaptic device. Additionally or alternatively, a tactile response can beprovided on the insertion device and/or on the endoscope holding suchinsertion device. At procedure 1935, any material and/or substance(e.g., a pharmacological agent, drug, filler, therapeutics, biologics,cellular materials, stem cells, genetic materials, immunotherapy agents,etc.) can be administered to the subject through the lumen or a biopsysample and/or other fluid, tissue, cells or material can be obtainedfrom the subject through the lumen.

As shown in the flow diagram of FIG. 19B, at procedure 1945, theinsertion device/apparatus can be inserted into the portion of thesubject to reach the tissue. At procedure 1950, an electrical signal canbe transmitted and/or received using an electrode formed on or in anouter surface of the shaft of the insertion device/apparatus. Atprocedure 1955, an impedance can be determined based on the electricalsignal. At procedure 1960, the tissue type can be determined based onthe impedance. Either the magnitude and/or phase components of theimpedance can be used to distinguish the tissue type by comparing themeasured values with known values (e.g., at one frequency or a narrowband of frequencies). In one exemplary embodiment, feedback may be givento the user by providing appropriate information to the user to anoptical display, auditory device or a haptic device. Additionally oralternatively, a tactile response can be provided on the insertiondevice and/or on the endoscope holding such insertion device. Atprocedure 1965, any material and/or substance (e.g., a pharmacologicalagent, drug, filler, therapeutics, biologics, cellular materials, stemcells, genetic materials, immunotherapy agents, etc.) can beadministered to the subject through the lumen or a biopsy sample and/orother fluid, tissue, cells or material can be obtained from the subjectthrough the lumen.

As shown in the flow diagram of FIG. 19C, at procedure 1975, theinsertion device/apparatus can be inserted into the portion of thesubject to reach the tissue. At procedure 1980, at least two electricalsignals can be received using at least two non-removable electrodesintegrated into the insertion device/apparatus. In one exemplaryembodiment of the present disclosure, the AC wave form that wasgenerated can pass through analog conditioner circuitry to theelectrodes. Impedance measurement of tissue between electrodes canimpact the wave form which can then be measured using exemplary digitalprocessing techniques (e.g., synchronous detection, 4fs, etc.) Atprocedure 1985, an impedance can be determined based on the at least twoelectrical signals. At procedure 1990, the tissue type can be determinedbased on the impedance. In one exemplary embodiment, feedback may begiven to the user by providing appropriate information to the user to anoptical display, auditory device or a haptic device. Additionally oralternatively, a tactile response can be provided on the insertiondevice and/or on the endoscope holding such insertion device. Atprocedure 1995, any material and/or substance (e.g., a pharmacologicalagent, drug, fluid (e.g. blood, plasma, and other fluids typicallyadministered through a needle), filler, therapeutic agents, cellularmaterials, stem cells, cells (e.g. adipocytes, lymphocytes, etc.),tissues (e.g. adipose tissue, bone marrow, etc.), genetic materials,immunotherapy agents, etc.) can be administered to the subject throughthe lumen or a material, tissue, cells, fluid and/or a biopsy sample canbe obtained from the subject through the lumen.

FIG. 19D shows an exemplary flow diagram of an exemplary method 1900′for determining a characteristic of a tissue of a patient, as well as aposition of a tip of the device with respect to the tissue, using theexemplary insertion device/apparatus. For example, as shown in FIG. 19D,at procedure 1905 a, an optically-transmissive layer is provided on theinsertion device/apparatus, e.g., on the base structure and/or on thecladding layer. At procedure 1910 a, the insertion device/apparatus canbe inserted into the portion of the patient to reach the tissue. Atprocedure 1915 a, a first optical signal can be transmitted-using theoptically-transmissive layer, which circumferentially surrounds the basestructure and/or the cladding layer of the insertion device/apparatus.At procedure 1920 a, a second optical signal can be received, e.g., fromthe tissue, via the optically-transmissive layer and/or via thecladding, whereas the second optical signal is based on the firstoptical signal. At procedure 1925 a, a location of the tip of theinsertion device/apparatus can be determined based on the informationprovided via the second optical signal and/or the determined location ofthe tip. At procedure 1930 a, the tissue characteristics can bedetermined based on the determined location of the tip and/or the secondoptical signal. In one exemplary embodiment, feedback may be given tothe user by providing appropriate information to the user to an opticaldisplay, auditory device or a haptic device. Additionally oralternatively, a tactile response can be provided on the insertiondevice and/or on the endoscope holding such insertion device. Atprocedure 1935 a, any material and/or substance (e.g., a pharmacologicalagent, drug, filler, therapeutics, cellular materials, stem cells,genetic materials, immunotherapy agents, etc.) can be administered tothe patient through the lumen or a material, fluid and/or a biopsysample can be obtained from the patient through the lumen.

In accordance with various exemplary embodiments of the presentdisclosure, it is beneficial to utilize the exemplary insertiondevice/apparatus to perform other exemplary procedures which aresignificantly benefitted with the identification of the tissue intowhich certain materials and/or substances are being inserted and/orinjected. FIG. 20A shows an exemplary illustration of the differ layersand sections within a tissue sample, and FIG. 20B provide and exemplaryillustration of an application of the exemplary embodiments of theinsertion devices/apparatuses according to the present disclosure whichcan be used the treatment of edematous fibrosclerotic panniculopathy(EFP), commonly known as cellulite, by an injection of an enzyme intothe tissue, such as, e.g., collagenase. For example, the enzyme can beinjected locally into the fat in order to break down the fibrous cords,also called septae which are responsible for causing the dimpledappearance of cellulite. The exemplary insertion device/apparatusaccording to the exemplary embodiments of the present disclosureincorporating and/or utilizing the exemplary impedance sensing asdescribed herein can be used to provide an indication and/or directionof when the tip of the insertion device/apparatus is within the fatbefore the injection. This beneficially facilitates the enzyme to beinjected close to the septae. The exemplary injection procedure is shownin FIG. 20B.

FIG. 20C illustrates an exemplary procedure involving a spinal puncture,which can be performed to diagnose the source of back, leg, neck, or armpain (diagnostic) and also to relieve pain (therapeutic). The exemplaryinsertion devices/apparatus incorporating impedance sensingfunctionality and/or configurations can be used to provide a user withan indication of when the tip of such exemplary insertiondevices/apparatus is within the epidural space. The exemplary insertiondevices/apparatuses (and/or a system connected thereto) can beprogrammed or otherwise configured to detect the unique impedancesignature and/or information indicative or representative of theepidural fluid. The exemplary insertion devices/apparatus also be usedfor an injection of various substances into the tissue, such as steroidsinto joints in the spine such as the sacroiliac joint, when theexemplary insertion devices/apparatus determines that a certain tissuetype or an opening is reached.

FIG. 20D shows an illustration of an exemplary procedure involving aninjection of substances (such as, e.g., platelet rich plasma (PRP)) intosynovial space of joints or cartilage of joints (e.g., knees, elbows,etc.), in accordance with the exemplary embodiment of the presentdisclosure. As illustrated in FIG. 20D, the exemplary insertiondevice/apparatus incorporating and/or utilizing the exemplary impedancesensing as described herein can provide an indication of when the tip ofthe exemplary insertion apparatus is within the space or cartilage. Theexemplary insertion devices/apparatuses (and/or a system connectedthereto) can be programmed or otherwise configured to detect the uniqueimpedance signature and/or information indicative or representative ofsynovial fluid or cartilage.

FIG. 23A shows an exemplary image showing the exemplary device beinginserted into a joint, according to an exemplary embodiment of thepresent disclosure. FIG. 23B shows an exemplary diagram of a joint,according to an exemplary embodiment of the present disclosure. Anincision in the skin can be made using surgical scissors to the exposestifle joint, the animal equivalent of a knee. The needle can beinserted through soft tissue at an angle into the stifle joint,primarily by feel. After holding the needle stationary, it can beadvanced to touch cartilage/bone. The needle can then be slowlywithdrawn. FIG. 23C shows a set of exemplary graphs illustratingreal-time feedback for two trials, according to an exemplary embodimentof the present disclosure. As the needle tip passes through differentbiological tissues and fluids, signals from the needle can be used tosense changes in very specific electrical properties. An exemplaryprocedure can be used to provide immediate response with real-time userfeedback. For example, feedback can be provided via any suitable wiredor wireless communication medium (e.g., Wi-Fi, Bluetooth, etc.) to anelectronic device (e.g., a smart phone, tablet, computer, etc.) or to aLED light embedded in the needle hub.

Further, for example, the exemplary insertion devices/apparatusesdescribed herein can be utilized in various cellulite treatmentapplications based on the detection of the unique impedance signatureand/or information of the tissue. Some of such exemplary applicationsare described in, e.g., U.S. Patent Publication No. 2018/0250217 andMichael P. Goldman et al., “Phase 2a, randomized, double-blind,placebo-controlled dose-ranging study of repeat doses of collagenaseClostridium histolyticum for the treatment of edematous fibroscleroticpanniculopathy (cellulite)”, Poster Presented at the 73rd Annual Meetingof the American Academy of Dermatology, Mar. 20-24, 2015; San Francisco,Calif., the entire disclosures are incorporated herein by reference.

In a further exemplary embodiment of the present disclosure, theexemplary insertion device/apparatus can be configured to be used toextract or aspirate bodily fluids, cells or tissues from a body,including, e.g., a subject. In one example, a syringe and needle can beused as the insertion device/apparatus to extract or aspirate materials,fluids, solutions, compounds, etc. which are well-known in the medical,dental and veterinary fields in general. Indeed, such exemplaryutilization of the insertion device/apparatus according to the exemplaryembodiments of the present disclosure can facilitate a greater precisionand safety for the subject. Non-limiting examples of use of theexemplary insertion device/apparatus can include phlebotomy proceduresused to draw blood samples, spinal taps used to extract cerebrospinalfluid from the spinal column, joint taps used to extract synovial fluid,needle biopsies to aspirate a sample of cells or tissue and theaspiration of bone marrow samples for typing and transplantation.

One having ordinary skill in the art may readily understand, based onthe review of the present disclosure, that such exemplary embodiment ofthe insertion device/apparatus may be used in the same or similar manneras other methods described in the present application in whichmaterials, cells, compounds, agents, enzymes, fillers, fluids, etc. areinserted into a body at certain determined tissues types, and instead byextracting or aspirating the targeted fluid, materials, compounds,agents, enzymes, fillers, fluids, etc. This can be done, in onenon-limiting example, by—instead of pushing the syringe plunger toexpunge a fluid or other materials—pulling back on the syringe plungerto create suction or a vacuum that draws the targeted fluid, materials,cells, compounds, agents, enzymes, fillers, fluids, etc. into thesyringe (e.g., in a reverse direction).

According to various exemplary embodiments of the present disclosure,the insertion device/apparatus and variants thereof described herein caninclude openings provided, e.g., in the cladding to act as side-looking“windows” to facilitate optical radiation to be transceived therethrough. Additionally, optical fibers can be provided along the basestructure, and the optical radiation can be provided through suchoptical fibers, together with or separately from the core 120 z, 120′,120″ and/or the cladding 170.

According to the exemplary embodiments of the present disclosure,exemplary materials that can be used for providing and/or forming thecoating/core and/or the cladding can include opticallyconductive/transmissive materials that can be applied to the targetstructures. The optical transmission coating can be applied by spraying,dipping, painting, sputtering, vapor deposition, etc. The exemplarymulti-layer structure (e.g., multiple core/cladding combinations) canalso be produced using, e.g., a co-extrusion process. Exemplarymaterials described herein can include polymers such as, e.g., urethane,acrylic, polycarbonate, polystyrene, cyclic olefin polymers orcopolymers, as well as copolymers combining materials. Silicones canalso be utilized. Glasses or ceramic coatings can be formed using a solgel process with post-processing such as sintering or by applying amaterial in powder form and then using a melt quenching process. Furtherexemplary materials can include silica glass, aluminum oxide amongothers. The exemplary materials can be selected based on the processtemperature and compatibility with the target structure. For example, aglass and/or ceramic that utilizes sintering for application may bedifficult to apply to a polymer as the temperatures may be above thepolymer glass transition temperatures. However, other exemplarymaterials can be easily utilized which are not effected by suchtemperature, and are within the scope of the present disclosure.

The material used for the cladding can include any material with a lowerrefractive index than the base transmissive coating. Such exemplarymaterials can include any of those listed above which have a slightlylower index than the material used for the core/coating. The claddingmay also include or be a reflective material such as, e.g., a metalliccoating.

The exemplary embodiments of the present disclosure can be used in, andnot certainly limited to, the following exemplary applications:

Tissue Sensing—Guidance, Diagnosis, Imaging

Using the exemplary embodiments of the insertion device/apparatusdescribed herein, it is possible to utilize light reflected and/orprovided from the tissue to characterize the type of tissue bycomparison with a database of known spectra. Exemplary applications caninclude, e.g., a) guidance of the insertion device/apparatus bydetermining the type of tissue provided at or near the tip of theinsertion device/apparatus, 2) diagnosis of the tissue by determiningwhether the information regarding the tissue identifies the tissue to benormal or abnormal (e.g., oncology or any clinical area looking atlive/dead tissue). It is also possible to select various opticalradiations based on consideration of the environment (e.g., tissue type,presence of blood, etc.) and/or consideration of depth of penetration.

Embolization—Fibroids, Tumors, Cerebral Aneurism, Hemostasis, FamilyPlanning, Etc.

The exemplary base structure with the central lumen (e.g., open, tubularstructure such as a needle or catheter) can be used to deliver a gel orcross-linkable monomer. The exemplary optical coatings (e.g.,waveguides) described herein can be used to deliver the opticalradiation with known characteristics based on the agent to polymerizethe delivered material. Thus, it is possible to achieve controlledpolymerization, which overcomes the deficiencies of the existingdevices, e.g., beads or other devices which are used to embolizestructures which are difficult to move after placement. Further, theexemplary integrated delivery insertion device/apparatus according tothe various exemplary embodiments of the present disclosure can reduceprocedure time and accuracy as there is no need to exchange orre-position multiple devices.

Photodynamic Therapy—Cancer, Etc.

The exemplary base structure with the central lumen (e.g., open, tubularstructure such as a needle or catheter) can be used to deliver aphotosensitizing agent. For example, exemplary optical coatings (e.g.,waveguides, cores, etc.) can be used to deliver the optical radiationdirectly to the area of the tissue where the photosensitizing agent wasdelivered with appropriate wavelength, power, etc. PDT typically relieson illumination using external light sources or lasers which limitstreatment to tissue depths of only ⅓^(rd) of an inch or less. Theexemplary embodiments of the present disclosure facilitate delivery andtreatment of deeper structures, anywhere the delivery/insertion devicecan penetrate, thus providing precise intra-tumor drug and lightdelivery.

Fillers—In-Situ Polymerization

The exemplary base structure with the central lumen (e.g., open, tubularstructure such as a needle, cannula or catheter) can be used to delivera filler pre-cursor—gel or cross-linkable monomer. For example,exemplary optical coatings (e.g., waveguides, cores, etc.) can be usedto deliver the optical radiation with known characteristics based on theagent to polymerize the material. Fillers are typically delivered infinal form which are viscous and difficult to deliver. Delivering amonomer or non-cross-linked gel, as described according to the exemplaryembodiments of the present disclosure facilitates delivery of a lessviscous material and also provide a clinician with the ability to shapethe structure and then polymerize to stabilize (shape).

Yet Further Exemplary Embodiments

FIG. 21A shows a block diagram of yet another exemplary embodiment of asystem according to the present disclosure. For example, exemplaryprocedures in accordance with the present disclosure described hereincan be performed by a processing arrangement and/or a computingarrangement 2102. Such processing/computing arrangement 2102 can be, forexample entirely or a part of, or include, but not limited to, acomputer/processor 2104 that can include, for example one or moremicroprocessors, and use instructions stored on a computer-accessiblemedium (e.g., RAM, ROM, hard drive, or other storage device).

As shown in FIG. 21A, for example a computer-accessible medium 2106(e.g., as described herein above, a storage device such as a hard disk,floppy disk, memory stick, CD-ROM, RAM, ROM, etc., or a collectionthereof) can be provided (e.g., in communication with the processingarrangement 2102). The computer-accessible medium 2106 can containexecutable instructions 2108 thereon. In addition, or alternatively, astorage arrangement 2010 can be provided separately from thecomputer-accessible medium 2006, which can provide the instructions tothe processing arrangement 2102 so as to configure the processingarrangement to execute certain exemplary procedures, processes andmethods, as described herein above, for example.

Further, the exemplary processing arrangement 2102 can be provided withor include an input/output arrangement 2114, which can include, forexample a wired network, a wireless network, the internet, an intranet,a data collection probe, a sensor, etc. As shown in FIG. 21, theexemplary processing arrangement 2102 can be in communication with anexemplary display arrangement 2112, which, according to certainexemplary embodiments of the present disclosure, can be a touch-screenconfigured for inputting information to the processing arrangement inaddition to outputting information from the processing arrangement, forexample. Further, the exemplary display 2112 and/or a storagearrangement 2110 can be used to display and/or store data in auser-accessible format and/or user-readable format.

FIG. 21B is a photograph of an exemplary embodiment of the exemplarysystem described herein above with reference to FIG. 21A. For example,the exemplary system incorporates electronics housed in a box which canbe a computing device 2150 or a data device, including but not limited amobile phone, tablet, etc. separate from the exemplary insertiondevice/apparatus 2160 (various exemplary embodiments described herein)and connected using a coaxial cable 2170 which can be terminated with aconnector that can provide an electrical contact with both the outerelectrical coating and the hypodermic needle tubing of the exemplaryinsertion device/apparatus 2160. The electronics incorporate an nRF52840System-on-Chip (SoC) is used to perform the analog to digitalconversion, digital signal processing and wireless communication. Theelectronics can communicate wirelessly with the computing device 2150 ordata device using wireless communication protocol(s), e.g., Bluetooth.The computing device 2150 can receive data, provide a real time displayof the measured impedance (both magnitude and angle), and/or record thedata.

FIG. 21C illustrates a measured response from the system duringinsertion into the inner thigh of a New Zealand White rabbit. Theexemplary insertion apparatus (e.g., a needle—exemplary structures ofwhich is described herein) was inserted through the skin and then guidedinto the femoral vein which was visible just below the skin. Blood couldbe seen inside the needle hub, verifying that the needle was inside thevein. The exemplary insertion apparatus was then held in place forseveral seconds and then advanced through the opposing vein wall intothe underlying muscle. Finally, the exemplary insertion apparatus waswithdrawn.

As shown in FIG. 21C which illustrates exemplary data, the measuredimpedance magnitude showed continuous changes as the needle was advancedthrough tissue and then into the femoral vein. The recorded valuesremained high, generally above 2,000 Ohms except for a brief time duringwhich the needle may have momentarily contacted a blood vessel. The datafor the initial insertion through skin into muscle, possible briefpassage through vessel is provided in FIG. 21B for period 2170. As theneedle entered the femoral vein (e.g., the needle held stationary), themeasured impedance magnitude dropped to a relatively steady valuebetween 1,500 Ohms and 2,000 Ohms for period 2175. As the needle wasadvanced through the vein and into muscle, the measured impedancemagnitude increased above 2,000 Ohms, as provided in period 2180. As theneedle was withdrawn, the measured impedance magnitude decreased brieflyas the needle tip passed back through the femoral vein and thenincreased as the needle was pulled out of the leg, as provided in period2185.

These exemplary results shown in FIG. 21C illustrate how an exemplarysystem may behave during a clinical application such as injection of afiller. In one example, the user can insert the exemplary insertionapparatus (e.g., needle) into a patient's/subject's face. A small ACcurrent passes from the hypodermic needle body through tissue or fluidin contact with the tip and then to the outer coating. The electronicsinfer impedance from the changes in the current caused during passagethrough the tissue or fluid. During initial insertion, the measuredimpedance magnitude will remain high. If the needle tip enters a bloodvessel in the face, the measured impedance magnitude will show adistinct drop. The electronics may be designed to detect when themeasured impedance magnitude is within a defined range, for example,between 1,000 Ohms and 2,000 Ohms. If the measured impedance magnitudeis within this exemplary range, the exemplary electronics and/or theexemplary electronic computing device as described herein below canprovide, e.g., an alert through the data device, for example an audibletone or a visual cue such as a light. Changes in, e.g., impedance angleor phase may also be used. The user may use the alert as an indicationthat the needle is in a blood vessel and/or that it may be unsafe toinject a filler.

This exemplary information can be used in other procedures, for example,during phlebotomy procedures, IV line placement, or catheterintroduction. The alert or another audio and/or visual indication can beused to let a user know that the needle is inside a vessel and that itis safe to proceed.

FIG. 21D illustrates a set of photographs of an exemplary embodiment ofthe exemplary system which integrates the electronics into the exemplaryneedle using light to provide a user with an alert. The exemplaryelectronics package clipped onto the exemplary needle making electricalcontact with the central needle body as well as the outer conductivecoating (image 2191), as described in various exemplary embodimentsprovided herein. The exemplary electronics shown in FIG. 21Dincorporate, e.g., a MSP430FR2355TRHA microcontroller by TexasInstruments. The exemplary microcontroller monitored the measuredimpedance and detected such measured impedance when the magnitude isbelow 1,500 Ohms (image 2192), between 1,500 Ohms and 5,000 Ohms (image2193), and above 5000 Ohms (image 2194). When the impedance is below1,500 Ohms, one set of LED lights are on as shown in the figure. Whenthe impedance is between 1,500 Ohms, and 5,000 Ohms, both sets of LEDlights are on with the intensity of the LED's varying with themagnitude. When the impedance is above 5,000 Ohms, the opposite set ofLED lights are on.

For example, FIG. 21D illustrates the exemplary operation during theexemplary needle insertion into a rabbit leg in what is believed to bethe femoral vein. For example, when the exemplary needle is insertedinto the vessel, one set of lights can be turned on and/or a particularaudible signal issued. When the needle is inserted into muscle, bothsets of lights are on and/or another audible signal issued. When theneedle is in tissue with higher impedance, the opposite set of lightsare on and/or still another audible signal issued.

It should be understood that the same or similar function can beachieved with a different number of lights or even with a single lightwith varying intensity, as well as various sounds, as well as or insteadof a combination of light(s) and sounds. It should also be understoodthat the exemplary instructions used to adjust the light can be adjustedto monitor for values below or above a particular threshold and/orwithin a particular range or following a particular sequence.

EXAMPLES Example 1. Impedance Phase Angle Defines Tissue Type

In-vivo testing was performed using fully integrated electrodes producedaccording to the pad printing procedure described above (see FIGS. 6 and7). Testing was performed in a live New Zealand White rabbit to measureimpedance in several different types of tissue. A cutdown was performedto expose major blood vessels in the rabbit's neck and thigh. Needleswere inserted into different tissues to different depths. Magnet wirewas used to connect the electrodes to an impedance analyzer (e.g.,Keysight 4294A/1D5). Measured impedance (e.g., magnitude and angle) wasexported to text files. FIG. 12A shows a set of exemplary diagrams andside views illustrating exemplary needle 1205 inserted into differenttissue types according to an exemplary embodiment of the presentdisclosure. The tissue types included dermis 1210, major blood vessels1215, and fat 1220.

FIG. 12B shows a set of exemplary graphs illustrating the impedancephase angle obtained as a function of frequency with the tip of theneedle inserted into different types of tissues according to anexemplary embodiment of the present disclosure. The impedance phaseangle was obtained as a function of frequency with the tip of the needleinserted into different types of tissues including dermis 1285, jugularvein 1255, and fat 1925. As shown in the graphs of FIG. 12B, themeasured phase angle varies with frequency. Dashed vertical lines anddashed horizontal lines superimposed onto the graphs are provided forreference and represent discrete frequency bands and phase anglethresholds that can be used for an exemplary sensing procedure. Darkvertical lines 1225 represent a band of frequencies from 50 kHz and 65kHz. Lighter vertical lines 1230 represent a band of frequencies from190 kHz to 250 kHz. Dark horizontal lines 1235 are placed at 158°. Lighthorizontal lines 1240 are placed at 167 degrees. As shown in graph 1285,when the exemplary needle is inserted into skin, the measured phaseangle 1250 remains below both dark vertical lines 1225 and lightvertical lines 1230 at all frequencies. As shown in graph 1290, when theexemplary needle is inserted into the jugular vein, the measured phaseangle 1255 exceeds the threshold defined by light horizontal line 1240in the lower band of frequencies. As shown in graph 1925, when theexemplary needle is inserted into fat, the measured phase angle 1260exceeds the threshold defined by the light horizontal line in the higherband of frequencies. The exemplary graphs shown in FIG. 15 indicate thatit is possible to set thresholds for phase angle in a specific, narrowband of frequencies to detect the difference between different types oftissue.

Example 2. Impedance Magnitude Defines Tissue Type

FIGS. 16-18 shows graphs illustrating exemplary results obtained usingthe exemplary insertion device/apparatus according to an exemplaryembodiment of the present disclosure. The exemplary insertiondevice/apparatus was inserted into different types of fresh tissueharvested from a pig and spectra of the measured magnitude and phaseangle were collected using an impedance analyzer. The exemplary graphsshown in FIG. 16 illustrate clear differentiation between the measuredimpedance magnitude response in various tissue as a function offrequency. Exemplary results showed a variation in response in differenttissues at different frequencies. The presence of an outer layer of PETheat shrink on the outside of the needles had little effect on therelative response. Frequencies that illustrate clear differences betweenthe measurements obtained for different tissues can be beneficial. Thesefrequencies can vary depending on the target tissue. Results indicatethat 1,000 Hz and 10,000 Hz provide sufficient response to differentiatefat from skin/muscle as there is a difference between the impedancemeasured in fat vs the measurements from other tissue types. The graphsillustrated in FIG. 17 illustrate that the exemplary impedance measuredover a very limited range, 1,000 Hz and 10,000 Hz can provide sufficientresponse to differentiate skin, fat, muscle, and that a single chipsolution can provide comparable relative responses to an analyzer.Exemplary results shown in graph 1705 were obtained using an exemplaryimpedance measurement chip while the results shown in graph 1710 wereobtained using a laboratory analyzer.

FIG. 18A shows an exemplary graph comparing the variation in impedancemagnitude obtained in a live Yucatan pig with exemplary electronics at asingle frequency, 10,000 Hz. Each symbol represents the pooled meanresult obtained from multiple continuous measurements. This same data istabulated in Table 1. The needle was removed and then reinserted aftereach measurement. Error bars represent the range above and below themean from two times the standard deviation, σ based on the pooledmeasurements. As there was no overlap of the results measured from fatas compared to dermis and muscle, this indicates that the exemplaryneedle system can sense the difference between fat and dermis/muscleusing measured impedance magnitude obtained from both instruments.Further, results indicate that measurements obtained at a singlefrequency, e.g., 10,000 Hz can be sufficient to resolve fat vs. dermisor muscle. Measured impedance magnitude can be pooled to obtain mean andstandard deviations for tissue and fluid types believed to correspond tomeasurements. Mean values are shown using square markers. Standarddeviations are illustrated with error bars.

TABLE 1 Combination of all results correlating to different tissues andfluids measured during in-vivo testing in a Yucatan pig provided pooledestimates for impedance magnitude Tissue Type Mean (ohms) Std Dev (ohms)Fat 1 13441.19 1332.923 Fat 2 5692.242 810.7929 Muscle 2983.11 204.831Blood 1576.659 268.8275 Filler 866.0706 81.88926

FIG. 18B shows an exemplary graph of the measured impedance magnitudeobtained from testing performed in a freshly excised Yorkshire pig leg,specifically tissue and fluid in and around the stifle joint which isroughly equivalent to a human knee. Data was collected using anexemplary system at a single frequency, 10,000 Hz. Each symbolrepresents the mean result obtained from multiple measurements. Thissame data is tabulated in Table 2. The needle was removed and thenreinserted after each measurement. Error bars represent the range aboveand below the mean from three times the standard deviation, σ based onthe pooled measurements. For a normal data set, the 3σ range containsapproximately 99.7% of the values. (See, e.g., Reference 7).

TABLE 2 Mean measured impedance magnitude collected from differenttissues and fluids measured during in-vitro testing in a freshlyharvested Yorkshire pig. 3× standard deviation also provided as anindication of scatter Tissue Type Mean (ohms) Std Dev (ohms) SynovialFluid 921 72 Muscle 2346 104 Vein 165 55 Tendon/Ligament 2759 252 Fat7767 763

Based on the exemplary data including, but not limited to, the datadescribed and/or incorporated herein, an exemplary device and/or systemcan monitor the measured impedance magnitude for values within specificranges to infer different tissue types or fluids. For the 26 Ga RWneedle coated with a 0.001 in thick layer of polyimide and with an outercoating of 0.001 in thick silver filled ink used to measure the data,the ranges of impedance magnitude are included in Table 3.

TABLE 3 Range of Exemplary Impedance Magnitudes in Tissue/FluidTissue/Fluid Type Impedance Magnitude (Ohms) Whole Blood 1,000 Ohms to2,000 Ohms Muscle 2,000 Ohms to 5,000 Ohms Fat 5,000 Ohms to 40,000 OhmsSynovial Fluid 200 Ohms to 1,000 Ohms

In addition to the specific needle size and materials, these are resultsspecific to one frequency, 10,000 Hz and one specific needle point.

FIG. 18C shows a set of exemplary graphs comparing the variation in themeasured impedance magnitude obtained with a laboratory analyzer at1,000 Hz with those obtained at 10,000 Hz. Each symbol 1825 representsthe mean result obtained from 10 measurements. The needle was removedand then reinserted after each measurement. Error bars 1830 representthe range above and below the mean from two times the standarddeviation, σ inferred from the 10 measurements. For a normal data set,the 2σ range contains approximately 95% of the values. (See e.g.,Reference 7). The results obtained at the two frequencies show similarbehavior. At both frequencies, the results obtained in fat show nooverlap in the range with those obtained from dermis and muscle. Thisindicates that measurements obtained at either 1,000 Hz or 10,000 Hz canprovide sufficient sensitivity to resolve fat vs either dermis ormuscle.

A person of skill in the art would recognize that changes to anexemplary needle geometry lead to a reduction in the measured impedancemagnitude. An increase in the needle gage or size increases the sensingarea and the amount of tissue in contact with the needle. For a fixedvoltage, more electrical current will appear to pass through the tissue,following Ohm's law. This will decrease the measured impedance magnitudewith a linear change tied to the change in the circumference of theneedle. Increasing the thickness of the insulating area will increasethe distance that the electrical current must pass through hence,increasing the amount of tissue in the electrical path. This will leadto a decrease in the measured impedance magnitude which will be linearlyproportional to the change in thickness. Similarly, a change in theneedle point will lead to a change in geometry, which will affect themeasured impedance magnitude. For example, decreasing the primary grindproduces a point with a shallower angle. Based on geometry, thisincreases the effective distance that electrical current must travel andincreases the amount of tissue that that the current must pass through.This can increase or decrease the measured impedance magnitude. Askilled practitioner would also recognize that a change in the frequencymay also alter the measured impedance magnitude or phase as a change infrequency will change the relative contributions of the resistance andreactance. Accordingly, depending on the features of the exemplarydevice, the range of impedance magnitude per tissue or fluid type can bereadily determined by a skilled practitioner according to the methods ofthe invention described herein.

The foregoing merely illustrates the principles of the disclosure.Various modifications and alterations to the described embodiments willbe apparent to those skilled in the art in view of the teachings herein.It will thus be appreciated that those skilled in the art will be ableto devise numerous systems, arrangements, and procedures which, althoughnot explicitly shown or described herein, embody the principles of thedisclosure and can be thus within the spirit and scope of thedisclosure. Various different exemplary embodiments can be used togetherwith one another, as well as interchangeably therewith, as should beunderstood by those having ordinary skill in the art. In addition,certain terms used in the present disclosure, including thespecification, drawings and claims thereof, can be used synonymously incertain instances, including, but not limited to, for example, data andinformation. It should be understood that, while these words, and/orother words that can be synonymous to one another, can be usedsynonymously herein, that there can be instances when such words can beintended to not be used synonymously. Further, to the extent that theprior art knowledge has not been explicitly incorporated by referenceherein above, it is explicitly incorporated herein in its entirety. Allpublications referenced are incorporated herein by reference in theirentireties.

EXEMPLARY REFERENCES

The following references are hereby incorporated by reference in theirentireties:

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1-19. (canceled)
 20. A method of determining a type of at least onetissue of at least one patient or if an orifice of the at least onetissue has been reached using an insertion arrangement and ablating theat least one tissue, the method comprising: inserting the insertionarrangement into at least one portion of the at least one patient toreach the at least one tissue; receiving a first electrical signal usinga first electrically conductive layer that at least partially surroundsa lumen of the insertion arrangement; receiving a second electricalsignal using a second electrically conductive layer that at leastpartially surrounds the first electrically conductive layer; determiningan impedance based on the first and second electrical signals;determining whether the type or the orifice of the at least one tissuehas been reached based on the impedance by comparing at least one of amagnitude of the impedance or a phase of the impedance withpredetermined values at one or more frequencies; based on thedetermination of whether the type or the orifice of the at least onetissue has been reached, ablating an area of the at least one tissue byapplying radio-frequency (RF) signals across the first and secondconductive layers to generate RF energy thereby heating or ablating thearea of the at least one tissue; and after the determination of whetherthe type or the orifice of the at least one tissue has been reached,administrating a substance near or at the area through the lumen. 21.The method of claim 20, further comprising electrically isolating thefirst electrically conductive layer from the second electricallyconductive layer using at least one insulating layer.
 22. The method ofclaim 20, further comprising obtaining a biopsy sample from the at leastone patient through the lumen.
 23. The method of claim 20, furthercomprising, based on the determination of whether the type or theorifice of the at least one tissue has been reached, providing at leastone current to at least one of the first electrically conductive layeror the second electrically conductive layer so as to generate an energyfield detectable by signals detectors which transmit locationinformation at least one portion of the insertion apparatus to acomputer hardware arrangement.
 24. The method of claim 20, furthercomprising determining a three-dimensional location of the at least oneportion of the insertion apparatus at or in a body based on the locationinformation.
 25. The method of claim 20, further comprising generatingan image on a display of the at least one portion of the insertionapparatus at or in a body in a three-dimensional space based on thelocation information.
 26. A method of ablating an area of at least onetissue of at least one patient using an insertion arrangement,comprising: a) inserting the insertion arrangement into at least oneportion of the at least one patient to reach the at least one tissue; b)receiving a first electrical signal using a first electricallyconductive layer that at least partially surrounds a lumen of theinsertion arrangement; c) receiving a second electrical signal using asecond electrically conductive layer that at least partially surroundsthe first electrically conductive layer; d) determining an impedancebased on the first and second electrical signals; e) determining whethera desired type or a desired orifice of the at least one tissue has beenreached based on the impedance; f) based on the determination ofprocedure (e), ablating the area of the at least one tissue by applyingradio-frequency (RF) signals across the first and second conductivelayers to generate RF energy thereby heating the area; and g) after thedetermination of procedure (e), administrating a substance near or atthe area through the lumen.
 27. The method of claim 26, furthercomprising, based on the determination procedure (e), providing at leastone current to at least one of the first electrically conductive layeror the second electrically conductive layer so as to generate an energyfield detectable by signals detectors which transmit locationinformation of at least one portion of the insertion apparatus to acomputer hardware arrangement.
 28. The method of claim 27, furthercomprising determining a three-dimensional location of the at least oneportion of the insertion apparatus at or in a body based on the locationinformation.
 29. The method of claim 27, further comprising generatingan image on a display of the at least one portion of the insertionapparatus at or in a body in a three-dimensional space based on thelocation information.
 30. A method of ablating an area of at least onetissue of at least one patient using an insertion arrangement,comprising: a) inserting the insertion arrangement into at least oneportion of the at least one patient to reach the at least one tissue; b)receiving at least one electrical signal using at least one electrodeformed on or in an outer surface of a shaft of the insertionarrangement; c) determining an impedance based on the at least oneelectrical signal; d) determining whether the type or the orifice of theat least one tissue has been reached based on the impedance; e) based onthe determination of procedure (d), ablating the area of the at leastone tissue by applying radio-frequency (RF) signals across the at leastone electrode to generate RF energy thereby heating the area; and f)after the determination of procedure (d), administrating a substancenear or at the area through a lumen of the insertion arrangement. 31.The method of claim 20, wherein the substance includes at least one (i)one or more pharmacological agent, (i) one or more biologics, (ii) oneor more fillers, (iii) one or more therapeutics, (iv) one or morecellular materials, (v) one or more stem cells, (vi) one or more geneticmaterials, or (vii) one or more immunotherapy agents.
 32. The method ofclaim 26, wherein the substance includes at least one (i) one or morepharmacological agent, (i) one or more biologics, (ii) one or morefillers, (iii) one or more therapeutics, (iv) one or more cellularmaterials, (v) one or more stem cells, (vi) one or more geneticmaterials, or (vii) one or more immunotherapy agents.
 33. The method ofclaim 30, wherein the substance includes at least one (i) one or morepharmacological agent, (i) one or more biologics, (ii) one or morefillers, (iii) one or more therapeutics, (iv) one or more cellularmaterials, (v) one or more stem cells, (vi) one or more geneticmaterials, or (vii) one or more immunotherapy agents.